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LETTERS TOTHE EDITOR
Postictal psychosis related regionalcerebral hyperperfusion
Postictal psychosis is a known complicationof complex partial
seizure in particulartemporal lobe epilepsy. It usually runs
abenign and self limiting course. A postictalphenomenon with focal
cerebral hypofunc-tion (similar to Todd’s palsy), rather
thanongoing seizure activity, has beenpostulated.1 2 Surface EEG is
either normalor showing non-specific slow waves.3
Hence,antipsychotic medications are prescribedinstead of
antiepileptic drugs. Until recently,the pathogenic mechanisms have
remainedunknown. In this communication, we reporton two patients
with postictal psychosis, dur-ing which a cerebral SPECT study
showed ahyperperfusion signal over the right temporallobe and
contralateral basal ganglion. Ashyperperfusion in ictal cerebral
SPECT isclosely linked to epileptic activities,4 our find-ings
support a contrary explanation forpostictal psychosis.
Prolonged video-EEG telemetry study wasperformed in patients who
underwent presur-
gical evaluation for epilepsy surgery. Antiepi-leptic drugs were
withdrawn to facilitateseizure recording. A diagnosis of
temporallobe epilepsy was based on analysis of theelectroclinical
events and, if applicable, post-operative outcome after anterior
temporallobectomy. Psychosis was diagnosed accord-ing to the fourth
edition of the diagnosticsand statistical manual of mental
disorders(DSM-IV) criteria of brief psychotic disorderswithout
marked stressor. HMPAO-SPECT wasperformed during the psychotic
period,which ranged from 2–4 days after the last sei-zure.
Interictal cerebral SPECT, brain MRI,and a Wada test were performed
as part ofpresurgical evaluation.
Patient 1 was a 34 year old Chinese womanwith complex partial
seizures since the age of18. Her seizure control was suboptimal on
acombination of antiepileptic drugs. BrainMRI showed a small
hippocampus on theright. Interictal EEG showed bilateral tempo-ral
sharp waves and ictal recordings con-firmed a right temporal
epileptogenic focus.A Wada test confirmed right hippocampalmemory
dysfunction. Six hours after her lastsecondary generalised
tonic-clonic seizureafter video-EEG telemetry, she began todevelop
emotional lability, talking nonsense,motor restlessness, and
auditory hallucina-tion. A cerebral SPECT study was performedat day
4 after her last seizure. Her psychoticfeatures persisted although
she was takingantipsychotic medication (pimozide). Cer-ebral SPECT
showed a clear hyperperfusion
signal over the right lateral temporal neocor-tex and
contralateral basal ganglion. Aninterictal cerebral SPECT study was
repeatedat 4 weeks after postictal psychosis whichshowed a complete
resolution of hyperper-fusion signal in the right temporal lobe
andbasal ganglia. Anterior temporal lobectomywas performed and she
became seizure freeafter surgery.
Patient 2 was a 44 year old man withintractable complex partial
seizures since theage of 30. His seizures were intractable
tomultiple antiepileptic drugs. Brain MRIshowed left hippocampal
sclerosis. Interictalcerebral SPECT showed a relative
hypoper-fusion area over the left hemisphere. Interic-tal surface
EEG was non-lateralising but ictalEEG disclosed a right hemispheric
onset. Onwithdrawal of antiepileptic drugs, sevencomplex partial
seizures with secondary gen-eralised tonic clonic seizures were
recordedwithin a period of 72 hours. His usualantiepileptic drugs
were then restarted.Thirty hours after his last secondary
general-ised tonic-clonic seizure; he began to developemotional
lability, talking nonsense, restless-ness, auditory hallucination,
persecutorydelusion, and delusion of superstition. Cer-ebral SPECT
study, performed 2 days laterwhile his psychotic features
persisted,showed two relative hyperperfused areas overthe right
temporal neocortex and contralat-eral basal ganglion in addition to
the originalhypoperfused area over the left hemisphere.An
antipsychotic agent (thioridazine) was
Interictal SPECT and SPECT performed during postictal psychosis.
(Top) A SPECT study of patient 1 showing areas of relative
hyperperfusion over theright temporal neocortex (red arrows) and
the left basal ganglia (blue and yellow arrows) during postictal
psychosis. (Bottom) SPECT study of patient 2showing areas of
hyperperfusion over the right temporal neocortex and the left basal
ganglia. Arrows indicate areas of hyperperfusion.
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started after the cerebral SPECT. Hispsychotic symptoms resolved
2 weeks laterwith full recovery.
Cerebral SPECT performed during theinterictal period (IP) and
during postictalpsychosis (PP) were analysed visually andareas of
hyperperfusion were identified.Quantitaive data at regions of
interest (ROIs)were measured on coronal and axial slidescontaining
basal ganglia (BG), mesial (MT),and lateral (LT) temporal lobe
structures.Asymmetry index (ASI) was calculated as((ROI focus−ROI
contralateral)/ROIfocus+ROI contralateral))×200%. We set
anarbitrary change of ASI >100% to be signifi-cant. As there
were only two patients, statisti-cal testing was not performed.
Both patients showed postictal psychosisand had a regional
increase in rCBF over theright temporal neocortex and the left
basalganglion compared with their interictal study(figure).
Quantitative analysis for patient 1showed changes of ASI during IP
and PPover right MT was +75% (-6.64476 to-1.65289); over the right
LT was +1167.8%(1.07527 to 12.55764); and over the left BGwas
+206.8% (-2.07373 to 2.21574). Quan-titative analysis for patient 2
showed changesof ASI during IP and PP over right MT was−3.8%
(13.14217 to 12.64158); over rightLT was +178.6% (10.4696 to
18.70027);and over left BG was +155.9% (−5.85556 to3.27522).
Postictal psychosis is a distinct clinicalevent associated with
temporal lobe epilepsy.1
The diagnosis of postictal psychosis requiresa close temporal
relation between bouts ofcomplex partial seizures and the onset of
psy-chosis. The psychosis usually develops after acluster of
complex partial seizures precipi-tated by abrupt withdrawal of
antiepilepticdrugs.1 The cluster occurs in patients withpoor drug
compliance or during video EEGtelemetry studies when antiepileptic
drugsare withdrawn purposefully. The clinicalcourse of postictal
psychosis is usually benignand predictable.1 5 In our patients,
theduration of psychotic disturbances lastedfrom 10 to 14 days,
which is in keeping withthe good prognosis. Antipsychotic
drugs,such as haloperidol and fluphenazin are usu-ally
prescribed.1
The underlying mechanism of postictalpsychosis is unknown.
Postictal cerebralhypofunction has been postulated as an ana-logue
to Todd’s paralysis after seizure.1 2
However, the presence of increased rCBFduring postictal
psychosis, may suggest analternative explanation as ictal SPECT
hasbeen shown to be highly sensitive and specificin demonstrating
seizure foci.4
To conclude, our results are contradictoryto the hypofunction
theory of Todd’s paraly-sis in postictal psychosis. We think that
thesehyperperfusion areas are responsible for thepostictal
psychosis. Further serial studies
with cerebral SPECT or PET may enhanceour understanding on the
mechanism of pos-tictal psychosis.
G C Y FONGK Y FONG
W MAKK L TSANGK H CHAN
R T F CHEUNGS L HO
Division of Neurology, University Department ofMedicine, The
University of Hong Kong
W Y HODepartment of Nuclear Medicine, Queen Mary
Hospital, Hong Kong
Correspondence to: Dr G C Y Fong, Departmentof Medicine, Queen
Mary Hospital, Pokfulam Road,Hong Kong email cyfong.medicine
@graduate.hku.hk
1 Savard G, Andermann F, Olivier A, et al. Postic-tal psychosis
after partial complex seizures: amultiple case study. Epilepsia
1991;32:225–31.
2 Morell F. Memory loss as a Todd’s paresis.Epilpesia
1980;21:185.
3 Kanner AM, Stagno S, Kotagal P, et al. Postictalpsychiatric
events during prolonged video-electro-encephalographic monitoring
studies.Arch Neurol 1996;53:258–63.
4 Ho SS, Berkovic SF, Newton MR, et al. Parietallobe epilepsy:
clinical features and seizurelocalization by ictal SPECT. Neurology
1994;44:2277–84.
5 Toone B. Psychoses and epilepsy. In: ReynoldsEH, Trimble MR,
eds. Epilepsy and psychiatry.London: Churchill Livingstone,
1981:113–7.
Oncofetal matrix glycoproteins incerebral arteriovenous
malformationsand neighbouring vessels
Cerebral arteriovenous malformations(AVMs) are thought to be
congenital lesionsexhibiting features of either mature
vascularwalls or embryonal anastomotic plexuses. It isgenerally
assumed that changes in size aredependent on enlargement of the
venouscompartment, organisation in the setting ofmicrohaemorrhages,
and gliosis. However,recent findings are consistent with
thehypothesis of ongoing angiogenesis.1 2
Previous research from this laboratorydisclosed that peculiar
isoforms of fibronectin(FN) and tenascin (TN) typically occur
infetal and neoplastic tissues.3–5 These isoformsare a blend of
structurally diVerent glycopro-teins that result from alternative
splicing of theprimary transcript and are mainly expressedin the
extracellular matrix. Their expression isundetectable in normal
adult tissues, with theexception of the vessels in the
regeneratingendometrium. To gain further insight into
thepathobiology of the AVMs the present reportsought to ascertain
whether these lesions alsoexpress oncofetal FN and TN isoforms.
Tissue samples were obtained after neuro-surgical excisions of
ruptured AVMs. All 10patients had experienced an
intracerebralhaemorrhage as the first clinical manifesta-
tion of their disease. There was no drughistory before bleeding.
Control specimensfrom two right gyri recti and one cerebellartonsil
were obtained, respectively, from op-erations for ruptured
aneurysms of the ante-rior communicating artery or for ArnoldChiari
disease.
Immunohistochemical evaluations wereperformed on 5 µm thick
cryostat sectionsusing a protocol reported previously.5 Owingto the
limited amount of available material,only in a few cases was some
fresh tissueretained to allow western blots. Distributionof FN and
TN isoforms was investigatedusing three monoclonal antibodies
(mAbs) ortwo Ab fragments, obtained by phage displaytechnology,
respectively. These Abs, preparedin our laboratory, were found to
work on freshfrozen material. According to the
previouscharacterisations the BC-1 mAb and theTN-11 Ab fragments
are specific for isoformsoccurring almost exclusively in fetal
tissuesand in tumours, with the recognised TN iso-form being
typically associated with anaplas-tic gliomas (table).
Control sections were processed identicallyto the other
specimens, but the primaryantibody was substituted with a
specificimmunoglobulin of recombinant antibodies.The antibodies
were blocked using the specificantigens. The antigens were
recombinant pro-tein containing the epitope produced in E Coli.For
the mAb BC-1 we used the recombinantprotein containing the type-III
repeats 7B-8–9.For the mAb IST-4 we used the recombinantprotein
containing the type-III repeats 2–8.For the recombinant antibodies
TN-11 andTN-12 the recombinant type-III repeat C andthe recombinant
fragment containing theEGF-like repeats were used,
respectively.
All 10 AVMs were found to contain largeamounts of FN and TN, as
shown by intenseimmunostaining with the use of the IST-9 /IST-4
mAbs and the TN-12 Ab fragment.The staining was localised either in
theendothelium or the subendothelial layer. Apositive response was
found in several artery-like vessels and in a few vessels with
thinnerwalls using the mAb BC-1. Staining with theTN-11 Ab fragment
showed occurrence oftype III repeat C TN isoform in the innerlayers
of the vascular components of thenidus, irrespective of their
morphology.
Six out of the 10 examined specimens werefound to contain
portions of cerebral tissuesurrounding the angiomatous nidus. In
allthese cases the wall of several vesselsexhibited intense
staining with the use of theTN-11 Ab fragment. Using the BC-1
mAbsome of these vessels exhibited some staining(figure). In the
control specimens (brain andcerebellum) both the FN isoform
containingthe ED-B sequence (ED-B+FN), and thetype III repeat C TN
isoform were absent,despite the widespread distribution of totalFN
and TN in the vascular walls.
Characterisation of the employed Abs and distribution of the
recognized isoforms.
Anti-FN mAbs4 5 Anti-TN Ab fragments3
IST-4 IST-9 BC-1 TN-12 TN-11
Recognised isoforms Total FN Isoforms containingthe ED-A
sequence
Isoform containing the ED-Bsequence
Total TN Type III repeat C Isoform
Distribution of the isoform (s) Widespread Widespread Absent in
adult tissues (with theexception of the
regeneratingendometrium)
Widespread Absent in adult tissues
Present in fetal tissues
Present in the vascular wall and thematrix of fetal tissues and
tumours
Absent in several types ofmalignancies
Present in the vascular wallof anaplastic gliomas
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Previous findings showed that ED-B+FNpresents with
conformational modifications inits central part and results from
deregulation ofFN pre-mRNA.4 The distribution of thisisoform was
found to be highly restricted innormal adult tissues. By contrast,
ED-B+ FNexhibited widespread distribution in the vascu-lature of
fetal tissues, including brain, and ofseveral types of
malignancies. It was thereforeregarded as a marker of
angiogenesis.5
Similarly, the type III repeat C TNisoform, recognised by the Ab
fragmentTN-11, was found to occur in the vascularwalls of
anaplastic gliomas. Northern blotanalysis showed that the mRNA of
thisisoform was undetectable in normal tissuesand some
malignancies, but was present inlarge amounts in fetal tissues,
includingbrain, and in glioblastomas3
Recent advances in the pathology of cerebralAVMs suggest that
these lesions might not bestatic. Tyrosine kinase, an endothelial
cell spe-cific receptor upregulated in glioblastomas,was found to
be highly expressed in bothAVMs and in the vessels of cerebral
tissue bor-dering the malformations, by contrast with thedown
regulation occurring in the vasculatureof the normal brain.1The
pattern of distribu-tion of structural proteins was consistent
withthe hypothesis of diVuse activation of angio-genesis, without
specific relation to individualvessel types.2
Furthermore, use of the cell proliferationmarker MIB-1 showed
endothelial prolifera-tion in arterioles, venules, and capillaries
ofthe cerebral tissue neighbouring AVMs.1
The present findings indicate that aparticular FN isoform,
mainly expressed bythe vasculature of fetal and tumorous tissues,as
well as a TN isoform typically detected inthe walls of vessels in
anaplastic gliomas, alsooccur in AVMs and in vessels of adjacent
cer-ebral tissue, but that both isoforms are absentin normal brain.
This evidence providesfurther support to the hypothesis of
ongoingangiogenesis in and around these lesions.
The presence of angiogenic features inAVMs might result from
maintenance of pro-liferating and remodelling potentials, or froma
specific response to haemodynamic stress invascular structures
subjected to increasedblood flow and pressure. Occurrence of
thesefeatures also in vessels lying in areas periph-eral to the
nidus might be related torecruitment of the neighbouring
vasculature,possibly dependent on focal ischaemia in thesetting of
arteriovenous shunting.1 2 However,the presence in apparently
normal vascula-ture of molecules typically occurring in
fetaltissues and malignancies indicate that cer-ebral AVMs may not
be static lesions. Furtherstudies are needed to ascertain whether
thisphenomenon results merely from haemody-namic stress or actually
reflects an intrinsicgrowth potential. Should this second be
thecase, current therapeutic strategies wouldpossibly require
revision.
This study was partially supported by theNational Research
Council (CNR), AIRCand the Ministry of University and
ScientificResearch (MURST). We thank Sergio De-seri, EE, for his
technical help and Mr. Tho-mas Wiley for manuscript revision.
ANTONIO PAUA DORCARATTO
G L VIALEDI S C A T Departement of Surgery, Division of
Neurosurgery, University of Genoa Medical School, SMartino
Hospital, Pad 2, Largo Rosanna Benzi 10,
16132 Genova, Italy
P CASTELLANIA SIRI
L ZARDILaboratory of Cell Biology National Cancer Institute,
Genoa, Italy
Correspondence to: Dr A Pau
1 Hatva E, Jääskeläinen J, Hirvonen H, et al. Tieendothelial
cell-specific receptor tyrosine ki-nase is upregulated in the
vasculature of arter-ovenous malformations. J Neuropathol ExpNeurol
1996;55:1124–33.
2 Rothbart D, Awad IA, Jiyon L, et al. Expressionof angiogenic
factors and structural proteins incentral nervous system vascular
malforma-tions. Neurosurgery 1996;38:915–25.
3 Carnemolla B, Castellani P, Borsi L, et al. Iden-tification of
a glioblastoma associated tn-c iso-form by a high aYnity
recombinant antibody.Am J Pathol 1999;154:1345–52.
4 Carnemolla B, Leprini A, Allemanni G, et al.The Inclusion of
type III repeat ED-B in thefibronectin molecule generates
conformationalmodifications that unmask a cryptic sequence.J Biol
Chem 1992;267:24689–92.
5 Castellani P, Viale G, Dorcaratto A, et al. Thefibronectin
isoform containing the ED-B on-cofetal domain: a marker of
angiogenesis. Int JCancer 1994;59:612–18.
Hashimoto’s encephalopathy presentingas “myxoedematous
madness”
The neuropsychiatric sequelae of hypo-thyroidism range from
lethargy and mentalslowing to the florid psychotic illness
referredto as “myxoedematous madness”. The lastcondition is
characterised by frank hypo-thyroidism accompanied by psychosis,
andmay respond completely to thyroxine.1 Morerecently described is
a syndrome of subacuteencephalopathy, associated with high titres
ofthyroid autoantibodies, raised CSF protein,EEG abnormalities, and
perfusion deficits inthe presence of normal structural
neuro-imaging.2–4 In most cases, the encephalopathyoccurs without
any gross change in circulat-ing concentrations of thyroid
hormones, sug-gesting that an inflammatory process isresponsible
for the cerebral dysfunction. Inthe absence of pathological data,
the evidencefor a specific pathogenetic mechanism islargely
circumstantial: a small vessel vasculitisand immune complex
deposition have bothbeen suggested.3 4
Although none of the published cases ofHashimoto’s
encephalopathy has describedpsychosis as a primary feature, it is
possiblethat “myxoedematous madness”, a conditionfirst described in
detail by Asher in 19491 liesin a range of encephalopathic
phenomenamediated by autoimmune mechanisms. Thissuggestion would
certainly be consistent withthe range of clinical presentations of
otherautoimmune cerebral vasculitides.5 As au-toimmune thyroiditis
is the commonest causeof thyroid failure in this country,6 it is
likely tohave been present in at least some of Asher’soriginal 14
cases. Although most had floridmyxoedematous features at
psychiatric pres-entation, this may simply reflect the diYcultyof
diagnosing subclinical thyroid diseasebefore rapid laboratory
assays became widelyavailable. Many features of the present
case,however, favoured an endocrine rather thanan inflammatory
mechanism, suggesting thatthe condition of “myxoedematous
madness”,though rare, remains a valid diagnostic entity.
A 63 year old market stallholder withoutmedical or psychiatric
history was brought toa local psychiatric hospital by the police.
Hisbusiness had been in decline for severalmonths, and his family
had noticed uncharac-teristic emotional lability. In the
weekspreceding admission he had experienceddelusions and
hallucinations, and exhibiteduncharacteristic behaviour. He had
reporteda vision of the crucifixion, and hearing thevoice of his
dead mother. He claimed that hishouse was occupied by the devil,
drovearound aimlessly in his car, and appearedconstantly fearful
and withdrawn. On the dayof admission he had made a bonfire in
thegarden and burned his wife’s clothes, familyphotographs,
furniture, and business papers.When his wife and son tried to
intervene he
Immunostaining with the TN-11 Ab fragment or the BC-1 mAb shows
the presence of the type IIIrepeat C TN-(A) and ED-B+ FN-(B)
isoforms in angiomatous vessels. These isoforms are alsopresent in
the wall of vessels of the cerebral tissue adjacent to the
angiomatous nidus (TN: C; FN: D).Bar=10 µm.
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became aggressive and threatened them witha saw. The general
practitioner was called andsuspected either an acute psychosis or
asevere depressive illness. Police assistance wasrequested because
of the patient’s continuingviolent behaviour.
On admission he was unkempt but coop-erative and apparently
euthymic. He denieddepression, but displayed no insight into
theirregularity of his behaviour. No psychoticfeatures were seen,
although during theadmission he consistently rationalised
allreported psychotic phenomena. He wasaggressive towards staV and
made repeatedattempts to abscond. General physical exam-ination was
unremarkable. Neurological ex-amination was normal except for
spokenlanguage, which was fluent and grammatical,but contained word
finding pauses, circum-locutions, and occasional semantic
errors(for example, “I just want to get my feet backon the table”).
Formal neuropsychologicaltesting, and a screen of laboratory tests
forreversible causes of encephalopathy, wereperformed on admission,
and results are pre-sented below (column A). Attention is drawnto
his mild naming deficit, and poorperformance on the Rey figure,
which wasdue to planning rather than visuospatialerrors, suggesting
a predominantly “dysex-ecutive” pattern. CT and EEG were
bothnormal, and SPECT disclosed widespreadbut mild cortical
hypoperfusion. Trifluop-erazine (2 mg twice daily) was started
onadmission, and thyroxine (75 µg once daily)added 1 week later.
His mental state andbehaviour stabilised, leading to dischargeafter
2 months.
At 6 month follow up the patient hadstopped neuroleptic drugs,
but continuedtaking thyroxine. He reported feeling “backto normal”,
had bought a new house, and wasworking as a part time shop
assistant. He stillhad subtle word finding diYculties, and
wasreferred to the regional memory clinic forfurther evaluation,
which took place 6months later. Behavioural assessment
showedpersisting deficits in delayed recall of verbalmaterial,
verbal fluency, and visuospatialfunction. Formal psychometric
testing, bloodtests, and SPECT were repeated, 1 year afterthe
original examinations. Laboratory andneuropsychological results are
presented inthe table. It is of note that, whereas his nam-ing
ability had improved, performance onfrontal executive tasks
remained impaired.The appearance of the follow up SPECT dif-
fered minimally, if at all, from the first exam-ination.
In summary, therefore, this patient pre-sented in clear
consciousness with a firstepisode of acute psychosis, and evidence
ofsubtle executive and linguistic neuro-psychological disturbance,
on the backgroundof gradual behavioural and aVective change.He was
profoundly hypothyroid due to anautoimmune thyroiditis, but there
was noclinical evidence of thyroid failure other thanthe abnormal
mental state. The psychiatriccomponent of his illness recovered
fully, andthe antithyroid microsomal antibody titre fellmarkedly
after thyroxine replacement, al-though his mild neuropsychological
deficitsremained unchanged. Corticosteroids werenot used at any
stage.
The response to thyroxine does not, initself, imply that the
cerebral illness had anendocrine origin; a recent report described
apatient with a subacute encephalopathicillness and compensated
hypothyroidism inthe presence of increased
antimicrosomalantibodies, all of which responded to thyrox-ine
replacement alone.4 In that case, however,both EEG and SPECT were
abnormal, theSPECT showing multiple areas of severelyreduced
perfusion, which normalised withtreatment. By contrast, in the
present case theEEG was normal and the SPECT abnormal-ity was
marginal and changed little, if at all,with treatment. The evidence
for a significantvasculitic component to the illness is,
there-fore, unconvincing.
The mild and relatively circumscribedneuropsychological deficits
coupled withflorid psychotic phenomena, also contrastwith the
profound global disturbance of cog-nition usually associated with
Hashimoto’sencephalopathy.3 This distinction suggeststhat
microvascular disruption and thyroidhormone depletion may emphasise
diVerentaspects of the clinical range in Hashimoto’sencephalopathy.
Although the present casewould support Asher’s conclusion that
thepsychiatric features of Hashimoto’s encepha-litis typically
respond to thyroid replacement,it additionally suggests that subtle
neuro-psychological deficits may be apparent evenin the absence of
obvious cerebral perfusiondeficits, and that these may not be
fullyreversible.
P GARRARDJ R HODGES
University of Cambridge Neurology unit,Addenbrooke’s Hospital,
Cambridge CB2 2QQ, UK
P J DE VRIESN HUNT
University of Cambridge Department of Psychiatry,Addenbrooke’s
Hospital, Cambridge CB2 2QQ, UK
A CRAWFORDJ R HODGES
MRC Cognition and Brain Sciences Unit, 15 ChaucerRoad, Cambridge
CB2 2EF, UK
K BALANDepartment of Nuclear Medicine, Addenbrooke’s
Hospital, Cambridge CB2 2QQ, UK
Correspondence to: Dr P Garrard, University ofCambridge
Neurology Unit, Box 165, Adden-brooke’s Hospital, Cambridge CB2
2QQ, UKemail [email protected]
1 Asher R. Myxoedematous madness. BMJ1949;555–62.
2 Thrush DC, Boddie HG. Episodic encepha-lopathy associated with
thyroid disorders. JNeurol Neurosurg Psychiatry
1974;37:696–700.
3 Shaw PJ, Walls TJ, Newman PK, et al.Hashimoto’s
encephalopathy: a steroid respon-sive disorder associated with high
anti-thyroidantibody titers: report of 5 cases.
Neurology1991;41:228–33.
4 Forchetti CM, Katsamakis G, Garron DC.Autoimmune thyroiditis
and a rapidly progres-sive dementia: global hypoperfusion onSPECT
scanning suggests a possible mech-anism. Neurology
1997;49:623–6.
5 Scolding NJ, Jayne DR, Zajicek J, et al. Cerebralvasculitis:
recognition, diagnosis and manage-ment. Q J Med 1997;90:61–73.
6 Dayan CM, Daniels GH. Chronic autoimmunethyroiditis. N Engl J
Med 1996;335:99–107.
Alien hand sign in Creutzfeldt-Jakobdisease
The clinical picture of Creutzfeldt-Jakob dis-ease (CJD)
includes various movement disor-ders such as myoclonus,
parkinsonism,hemiballism, and dystonia. We report on apatient with
CJD who manifested the alienhand sign. We suggest that CJD should
beincluded in the diVerential diagnosis ofdiseases which present
with an alien hand.
Creutztfeldt-Jakob disease, one of thehuman prion diseases, is
characterised byrapidly progressive mental and motordeterioration.1
Involuntary movements occurin above 90% of the patients in the
course ofthe disease, the most common beingmyoclonus.1 Other
movement disordersrange from tremor to chorea, athetosis,dystonia,
and hemiballism.1 We report on apatient with CJD who presented with
an alienhand.
Alien hand is a rare and striking phenom-enon defined as “a
patient’s failure to recog-nise the action of one of his hands as
his own”.2
One of the patient’s hands acts as a stranger tothe body and is
uncooperative. Thus, there isloss of feeling of ownership but not
loss of sen-sation in the aVected hand. Originally de-scribed in
callosal tumours,3 the aetiology ofalien hand also includes
surgical callosotomy,4
infarction of the medial frontal cortex, occipi-totemporal lobe,
and thalamus,1 5 infection,6
and corticobasal degeneration.5 7
A 70 year old, right handed Jewish manborn in Argentina, living
in Israel for the past20 years, was admitted to the
NeurologyDepartment. Until a month before hisadmission, he was
apparently healthy andhelped in the accounting oYce of the
villagewhere he lived. His neurological illness hadpresented
insidiously during the past monthwith unsteadiness of gait and
frequent falls.He also manifested behavioural changes,became
aggressive, and had visual hallucina-tions, perceiving insects and
mice movingthrough his visual field. Often, he expressedhis fear
from seeing that the “ceiling was
Table 1 Laboratory and neuropsychological results at
presentation (A) and at 12 month follow up (B)
Laboratory (units) A B
Full blood count Normal NormalErythocyte sedimentation rate 12
6Urea and electrolytes Normal NormalLiver function tests Normal
NormalAntinuclear antibody Negative NegativeB12 and folate Normal
Not testedVDRL Negative Not testedThyroid stimulating hormone
(mU/l) 58.4 0.87Free T4 (pmol/l) 7.4 Not testedAntithyroid
microsomal antibody titres 1:25600 1:1600Psychometric
(normal/predicted range):
Folstein MMSE (>24) 25/30 25NART IQ 10th percentile 18th
percentileWAIS-R (verbal) 13th percentile Not testedWAIS-R
(performance) 27th percentile Not testedFAS verbal fluency (>30)
25 23Cognitive estimates test (15) 10/30 16/30Digit span forwards
(>5) 7 6Rey-Osterreith complex figure (copy) (36) 25.5
24Rey-Osterreith complex figure (recall) ( 30%) Not tested 75%
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falling over him”. His wife mentioned bizarre,useless movements
of his left hand whichwere present from the beginning of
thedisease.
On admission, he was awake, brady-phrenic, and partially
collaborative. His con-versation was often disrupted by
hallucina-tions. The aVect was sad and he had partialinsight for
his mental dysfunction. He wasdisoriented for time, place, and
situation. Hecould understand speech and was able to fol-low oral
instructions involving two consecu-tive components. Naming was
preserved.Prominent dysgraphia and dyscalculia werenoticed.
Immediate recall and short termmemory were severely disturbed,
whereaslong term memory, especially for personal lifeevents, was
relatively spared. Abstract think-ing was severely aVected.
Bimanual move-ments, such as clapping, were extremely diY-cult.
The cranial nerves were normal as wereocular fundi. The motor
examination showednormal force. Deep reflexes were symmetricand
plantar responses were flexor. The rightarm had a dystonic posture.
His gait wasataxic on a wide base.
At times, the left arm would spontaneouslyrise in front of the
patient during speaking orwhile using his right hand. He was
unaware ofthese movements until they were brought tohis attention.
When questioned about theirpurpose, the patient denied that they
werevoluntary. No grasping of either hand or footwas found. The
patient had no corticalsensory loss.
The laboratory data including blood chem-istry, haematology, and
sedimentation ratewere normal, as were folic acid, vitamin
B12concentrations, and thyroid function.Vene-real disease research
laboratory and HIV testswere negative. The cerebrospinal fluid
hadnormal content. Brain CT showed mildcerebral atrophy. An EEG
showed severe dif-fuse slowing at admission. Within a week,repeated
EEGs showed triphasic waves with aperiodic pattern of 1- 1.5
Hz.
During the next 2 weeks, the patient devel-oped myoclonic jerks.
Severe dysphasia andcognitive decline were accompanied by
con-fusion and aggression. He became grosslyataxic, and unable to
walk and perform any ofhis daily activities even with help.
Transferredto a chronic care hospital, he died few weekslater.
Postmortem examination was not al-lowed.
This short fatal neurological disease mani-fested by fulminant
dementia, myoclonicjerks, and extrapyramidal and cerebellar
dys-function was strongly suggestive of CJD. Theperiodic EEG
pattern reinforced this diagno-sis. Our patient’s alien hand was
part of theotherwise characteristic clinical picture ofCJD, but it
occurred early in the diseasecourse when no myoclonic jerks
werepresent. We are aware of only one report ofalien hand in CJD.
MacGowan et al8
described two patients with CJD with amyoclonic alien hand
syndrome. In onepatient the left arm “was noted to havespontaneous
movements which appearedpurposeful...wandered out of her view”.
Inthe second, the alien limb performed com-plex actions such as
unbuttoning her blouseand removing a hair pin. Although ourpatient
had no myoclonus or pyramidal signswhen the alien hand appeared, in
theirpatients it was associated with spontaneousor stimulus
sensitive myoclonus, spastichemiparesis, and cortical sensory
loss.
The literature seems to describe distinctforms of alien hand.
All share the occurrenceof involuntary movements contrary to
thepatient’s stated intent, but the types of move-ment diVer. In
the callosal form, there arepurposeful movements of the
non-dominanthand.9 In the frontal form, there is graspingand
utilisation behaviour of the dominanthand.9 In the corticobasal
degeneration, thereare aimless movements of either hand.5 7
When a consequence of tumorous or vascularpathology,9 alien
hands can perform complexacts such as trying to tear clothes or
undoingbuttons. The description by MacGowan et al8
has characteristics of the callosal form (espe-cially in patient
2). However, our casesuggests that the alien hand sign in CJD
mayappear in a diVerent type, performing lesscomplex movements
which resemble thosereported by Riley et al in
corticobasaldegeneration.7 These authors described thealien limb as
“ involuntarily rising and touch-ing the mouth and eyes” (patient
1). Thepatient thought that she “was powerless tostop this
movement” and when directed tostop responded that “she can’t”.
Anotherpatient’s left arm was at times “elevated infront of him”,
while he was “unaware of thissituation until his attention was
called to it”(patient 10).
Another related phenomenon coined as“arm levitation” was
reported in progressivesupranuclear palsy. In these patients the
arminvoluntarily raised and performed semi-purposeful
movements.10
One common denominator between CJD,corticobasal degeneration,
and progressivemultifocal leukoencephalopathy,6 in which analien
hand sign has also been described, ismultifocality. In corticobasal
degeneration, itwas proposed that more than one site isaVected or
that a “release” phenomenonoccurs accounting for the aetiology of
alienhand.7 In CJD, bilateral cortical damage tomotor areas might
be the origin of their sub-sequent isolation and disconnection.
We suggest that CJD should be added tothe diVerential diagnosis
of diseases present-ing with an alien hand with or without
myo-clonus.
We are indebted to Professor Eran Zardel, Depart-ment of
Physiology, University of California, LosAngeles, USA.
R INZELBERGP NISIPEANUS C BLUMENR L CARASSO
Department of Neurology, Hillel YaVe Medical Center,Hadera,
Israel
Correspondence to: Dr Dr R Inzelberg, Depart-ment of Neurology,
Hillel YaVe MedicalCenter, Hadera, 38100, Israelemail
[email protected]
1 Brown P, Gibbs CJ, Rodgers-Johnson P, et al.Human spongiform
encephalopathy: the Na-tional Institutes of Health series of 300
cases ofexperimentally transmitted disease. Ann
Neurol1994;35:513–29.
2 Levine DN. The alien hand. In: Joseph AB,Young RR, eds.
Movement disorders in neurologyand neuropsychiatry. Oxford:
Blackwell, 1999:645–9.
3 Brion S, Jedynak CP. Troubles du transfertinterhemispherique.
A propos de trois observa-tions de tumeurs du corps calleux. Le
signe dela main etrangere. Rev Neurol 1972;126:257–66.
4 Bogen JE. The callosal syndromes. In: HeilmanKM, Valenstein E,
eds. Clinical neuropsychology.2nd ed. New York: Oxford University
Press,1985:295–338.
5 Doody RS, Jankovic J. The alien hand andrelated signs. J
Neurol Neurosurg Psychiatry1992;55:806–10.
6 Berger JR, Concha M. Progressive
multifocalleukoencephalopathy: the evolution of a diseaseonce
considered rare. Journal of Neurovirology1995;1:5–18.
7 Riley DE, Lang AE, Lewis A, et al. Cortical-basal ganglionic
degeneration. Neurology 1990;40:1203–12.
8 MacGowan DJL, Delanty N, Petito F, et al. Iso-lated myoclonic
alien hand as the sole presen-tation of pathologically established
Creutzfeldt-Jakob disease: a report of two patients. J
NeurolNeurosurg Psychiatry 1997;63:404–7.
9 Feinberg TE, Schindler RJ, Gilson Flanagan N,et al. Two alien
hand syndromes. Neurology1992;42:19–24.
10 Barclay CL, Bergeron C, Lang AE. Arm levita-tion in
progressive supranuclear palsy. Neurol-ogy 1999;52:879–82.
Recurrent peripheral neuropathy in agirl with celiac disease
The involvement of the peripheral nervoussystem (PNS) in
children with celiac diseaseis particularly rare. Furthermore, in
bothchildren and adults with celiac disease,neurological
complications are chronic andprogressive.1
We report on a 12 year old girl aVected byceliac disease, who on
two separate occasionspresented with an acute peripheral
neurologi-cal syndrome after accidental reintroductionof gluten in
her diet.
This patient was born uneventfully tohealthy non-consanguineous
parents with nofamily history of neurological or metabolicdiseases.
At the age of 6 months she wasdiagnosed as having celiac disease
accordingto the European Society of Paediatric Gastro-enterology
and Nutrition (ESPGAN) crite-ria. Since then she was on a strict
gluten freediet and was asymptomatic until the age of 10years when
severe diarrhoea, vomiting, andabdominal pain manifested 6 days
after theintake of corn flakes erroneously thought tobe gluten
free. No previous infections hadbeen noticed. One week after the
onset ofthese symptoms she experienced acute weak-ness and pins and
needles sensation confinedto her legs. At that time her parents
stoppedher intake of corn flakes on the suspicion thatthese were
responsible for the symptoms.Despite this, symptoms worsened during
thenext 2 days, confining her to bed.
At hospital admission, she was alert andmentally stable. Results
of general physicalexamination were unremarkable. Neurologi-cal
examination disclosed symmetric, pre-dominantly distal, weakness of
the legs; theknee jerks and ankle reflexes were depressed;plantar
reflexes were flexor. Distal stockingglove decreased in pin prick
and temperaturewith sparing of propioception and lighttouch.
Coordination tests were normal.
Laboratory investigations showed a whitecell count of 9300/mm3.
The results of thefollowing investigations were within thenormal
limits: haemogram, erythrocyte sedi-mentation rate, serum urea,
nitrogen, electro-lytes, creatinine, glucose, transaminase,
bi-lirubin, immunoglobulins (Igs), lead, iron,copper, urinalysis,
urinary porphyrin, folicacid, and vitamins A, B1, B6, B12, and E.
Anti-bodies to Campylobacter jejuni, neurotropicantivirus
antibodies, specific and non-specificorgan autoantibodies, IgA and
IgG antiglia-din antibodies (AGAs), IgA antiendomesiumantibodies
(EMAs), and IgA antireticulumantibodies (ARA), assayed by enzyme
linkedimmunoadsorbent assay (ELISA) and im-munofluorescence (IF)
were also negative.Lumbar puncture was not performed. Anti-bodies
against gangliosides GM1 and GQ1b,myelin associated glycoprotein
and myelin
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basic protein were not tested. Nerve conduc-tion studies were
consistent with a predomi-nately motor demyelinating peripheral
neu-ropathy (table). Her symptoms improvedspontaneously and she was
discharged homeafter 2 weeks. For 2 years she was asympto-matic on
a gluten free diet.
At the age of 12 she presented acutely withsevere abdominal pain
8 days after a weeklyintake of bread meant to be gluten free.
Twoweeks later, due to persisting gastrointestinalsymptoms, her
parents excluded the breadfrom her diet. After 2 further weeks,
while theabdominal pain was gradually improving, shehad a new
episode of acute weakness in thelower limbs and sensory
abnormalities in-cluding burning paraesthesiae. On neurologi-cal
examination the legs showed markeddiminution in muscle power;
absent deeptendon reflexes, and a reduction in pain andtemperature;
light touch, perception of posi-tion, and vibration were preserved.
Walkingwas impaired and the patient was bedridden.Otherwise the
examination was normal.
A haemogram showed white cell counts of9700/mm3. Laboratory
investigations werewithin normal values as in the past. IgA andIgG
AGA, IgA EMA, and IgA ARA assayedby ELISA and IF were again
negative. Nerveconduction studies confirmed the presence ofa
predominantly motor demyelinating neu-ropathy (table). The parents
refused consentfor a lumbar puncture or nerve biopsy.
Over the next 2 weeks her neurological dis-abilities
spontaneously improved until fullrecovery was complete. After 4
weeks, AGA,EMA, and ARA were still negative.
On her most recent admission, 1 year afterthe onset of her first
neurological symptoms,she is still on a strict gluten free diet and
hasno residual symptoms or signs.
The natural history of celiac disease is wellknown and the
typical celiac enteropathy isoften associated with several other
disorders.However, as celiac disease is a relatively com-mon and
lifelong condition, it is likely thatsome of these associations may
occur bychance.
This patient, who was diagnosed as havingfrank celiac disease at
the age of 6 months,experienced two episodes of acute
peripheralneuropathy, at the age of 10 and 12 years,respectively.
Two major pieces of evidencestrongly support the assumption of a
glutenderived disease: (1) the episodes occurred onboth occasions
when gluten was accidentallyreintroduced in the diet; and (2) the
responseto a gluten free diet was reasonably rapid,occurring within
weeks.
The present case, however, diVers clinicallyfrom those with
neurological involvement pre-viously reported. In the paediatric
age group,
in fact, neurological complications of celiacdisease are rarely
encountered and are mostlyconfined to the CNS2: to the best of
ourknowledge, there are only two previouslyreported cases of PNS
involvement in childrenwith celiac disease. In both cases,
however,these were chronic axonal polyneuropathiespresenting during
a gluten free diet.3 4
In both episodes in the present case neuro-physiology was
strongly supportive of ademyelinating peripheral neuropathy,
whichis most commonly attributed to a directimmune mediated attack
to the myelin. Bycontrast, wallerian and axonal degenerationmay be
caused by vasculitis, and nutritional,metabolic, and toxic
factors.
An autoimmune pathogenesis in associ-ation with strong evidence
of a geneticsusceptibility has been proposed for celiacdisease.
Although it is well established thatAGA, EMA, and ARA are reliable
indicatorsof sensitisation to gluten at least at the time
ofdiagnosis, in the clinical practice at follow up,during a gluten
challenge, pathological valuesof these antibodies may not be
detected.5 Inthe present case the time course of the diseasemight
be suggestive of an antibody mediatedresponse. However, we could
not detectpathological concentrations of AGA, EMA,or ARA antibodies
either during the course ofthe disease or at follow up.
It is known that in celiac disease manyimmunological
perturbations can occur out-side the gastrointestinal tract.
Crossing of theantigens through a damaged small intestinalmucosa,
deposition of immune complexes intarget organs, a reduction in
immune surveil-lance, mechanism of molecular mimicry, andactivated
T cell response may contribute tothe pathogenesis of the diseases
associatedwith celiac disease. Direct toxic eVects ofgliadin and
vitamin deficiency are other pos-sible pathogenic mechanisms of
damage tothe nervous system. Although we ruled out avitamin
deficiency it is still questionablewhether a toxic neuropathy can
be the case.
In conclusion, this case shows two majorissues: an acute
polyneuropathy can be acomplication of celiac disease in
childhoodand its benign course could help in theunderstanding of
the underlying pathogenicmechanisms.
We are grateful to Professor Angela Vincent(Oxford) for her
helpful suggestions in reviewing themanuscript.
AGATA POLIZZIMARIA FINOCCHIARO
ENRICO PARANOPIERO PAVONE
Division of Paediatric Neurology, Department ofPaediatrics,
University of Catania
Catania, Italy
SALVATORE MUSUMECIDepartment of Paediatrics, University of
Sassari,
Sassari, Italy
AGATA POLIZZINeurosciences Group, Institute of Molecular
Medicine,
Department of Clinical Neurology, University ofOxford, Oxford,
UK
Correspondence to: Dr Agata Polizzi, Division ofPaediatric
Neurology, Department of Paediatrics,University of Catania, Viale A
Doria 6, 95125Catania, Italy email: [email protected]
1 Cooke WT, Thomas Smith W. Neurologicaldisorders associated
with adult coeliac disease.Brain 1966;89:683–722
2 Gobbi G, Bouquet F, Greco L, et al. Coeliacdisease, epilepsy
and cerebral calcifications.Lancet 1992;340:439–43
3 Papadatou B, Di Capua M, Gambarara M, et al.Nervous system
involvement in paediatric coe-liac patients. In: Mearin ML, Mulder
CJJ, eds.Coeliac disease. Dordrecht: Kluwer
Academic,1991:199–203.
4 Simonati A, Battistella PA, Guariso G, et al.Coeliac disease
associated with peripheral neu-ropathy in a child: a case report.
Neuropediatrics1998;29:155–8
5 Bottaro G, Sciacca A, Failla P, et al. Antigliadinantibodies
in the various stages of coeliacdisease in children. Pediatr Med
Chir 1988;10:409–13
Frontal release signs in older peoplewith peripheral vascular
disease
A growing body of research examiningneurological aspects of
clinically “silent” cer-ebrovascular disease suggests that
neurologi-cal signs indicative of generalised organicbrain damage
may occur in the absence ofcompleted stroke.1 These soft signs
includeprimitive reflexes (frontal release signs), rep-resenting an
anatomical and functional deaf-ferentation of cortical from
subcortical struc-tures. Primitive reflexes are known to occur ina
wide variety of dementias, includingAlzheimer’s disease2 and
vascular dementia.3
It is likely that the presence of undetectedcerebrovascular
disease accompanying pe-ripheral vascular disease is
underestimated,as peripheral vascular disease is known to bea risk
factor for transient ischaemic attacks. Astudy assessing 373 older
patients withperipheral vascular disease found that 72 ofthe 144
patients who had not experienced atransient ischaemic attack or
stroke werefound to have a degree of carotid stenosis ofbetween 60%
and 99%.4
In the present study, the prevalence ofprimitive reflexes was
examined in older peo-ple with peripheral vascular disease and
anon-vascular control group. Independentpredictors of these
reflexes were also exam-ined in peripheral vascular disease.
Bothgroups were drawn from the same geographi-cal area. All were
interviewed and examinedoutside hospital by myself. Interviewees
werecommunity residents from the catchmentarea of an inner city
London teaching hospi-tal.
Twenty five consecutive non-amputees onthe waiting list for
femoropopliteal bypassoperation were compared with 25
postopera-tive patients who had undergone elective hipor knee
replacement and a period of inpatientrehabilitation. All
participants were aged 65and over at the time of interview.
Patientswith peripheral vascular disease all had clini-cal and
Doppler proved evidence of periph-eral ischaemia. Controls were
interviewedbetween 6 months and 1 year after theiroperation. Both
groups had no history ofstroke or transient ischaemic attack.
A more detailed description of instrumentsis provided
elsewhere.1 All subjects were
Electrophysiological study suggestive in both episodes of an
acute demyelinating peripheral neuropathyconfined to the lower
limbs. Values were within normal limits in the upper limbs
1st Episode 2nd Episode
Peroneal LR TibialL
R PeronealL
R TibialL
R
MCV (ms) 26 27 22 2424 28 20 23
DL (ms) 7.3 8.0 7.2 8.87.5 8.4 7.0 9.0
F wave latency (ms) 70 72 83 84CMAP (µV) 3 2.7
Sural LR SuralL
R
SCV (ms) 38 4042 41
AMP (µV) 16.2 17.416.8 18
MVC=motor conduction velocity; DL=distal latency; CMAP=compound
motor action potential;SCV=sensory conduction velocity;
AMP=amplitude; L=left; R=right.
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examined using a rating scale for theexamination of frontal
release signs (FRSS),with nine operationally defined items, eachon
a seven point semiquantitative scale. Thenine reflexes were
paratonia and palmomen-tal, hand grasp, foot grasp, glabellar,
rooting,snout, and visual/tactile sucking
reflexes.Neuropsychological measures included theassessment of
frontal lobe function (trailmak-ing tests A and B, behavioural
dyscontrolscale, and the controlled word associationtest) and
generalised cognitive impairment(CAMCOG). Depression was assessed
usingthe Hamilton rating scale for depression, 15item geriatric
depression scale, and diagnos-tic criteria for DSM IV major
depressive dis-order. Family history of depression, wish todie, and
suicidal ideation within the past yearwere also recorded, as were
blood pressureand a checklist for chronic physical illness.
Total FRSS scores and scores on FRSSsubscales were compared
between groupsusing the Mann-Whitney U test for inde-pendent
samples. In the peripheral vasculardisease group, a correlation
matrix for totalFRSS score against DSMIV depression,CAMCOG score,
behavioural dyscontrolscale score, verbal fluency score
(totalnumber of words beginning with F, A, and S)and trailmaking
test times was examinedusing the Spearman correlation
coeYcient,controlling for age, sex, blood pressure, andchronic
physical illness. Behavioural dyscon-trol scale scores, trailmaking
A/B test times,and verbal fluency scores were first convertedinto
binary variables according to whetherthey were at/above or below
the median valuefor the group. CAMCOG score was dividedinto
subjects scoring 69 or above or less than69. Those associations
with a two tailedsignificance of 0.1 or less were then enteredinto
a linear regression equation using thestepwise method.
Patients with peripheral vascular diseasehad a higher mean score
on the frontal releasesigns scale than controls (5.8 (SD 4.6) v
1.7(SD 1.9)) (Mann-Whitney U=144.500,Z=−3.33, two tailed p=001), as
well as onglabellar and rooting reflexes (table). Onlyone variable
(trailmaking B test time) wasentered into the equation; this
accounted for23% of the variance in FRSS score (B=4.6,95%
confidence interval (95% CI) (B)1.3–8.0, p=0.01).
In peripheral vascular disease, there is lim-ited information
available concerning theintellectual and neurological sequelae
ofcoexisting cerebrovascular disease. Phillips etal found greater
impairment in psychomotorspeed and abstract reasoning in patients
withperipheral vascular disease than age/sexmatched controls, with
less significant diVer-ences between the groups in verbal
fluency,concentration, abstract thought, perception,and
constructional skills.5 Another study bythe same group found poorer
performance inpatients with peripheral vascular disease
thancontrols on visual memory, trailmaking Btest, and visuospatial
skills. Patients withperipheral vascular disease were also
equallyimpaired in these areas compared with amatched group of
stroke patients.6
Small numbers of patients, which may alsohave obscured other
significant findingsbetween the two groups, limit the presentstudy.
However, there is some evidence thatclinically relevant
cerebrovascular diseasemay accompany peripheral vascular diseaseand
that concomitant disruption of frontal/subcortical brain function
may not presentwith hard neurological signs. As it is possiblethat
silent brain infarction was present inpatients with peripheral
vascular disease, fur-ther studies incorporating brain imaging
arerequired before there can be a clearer under-standing of the
relation between peripheraland central vascular pathology.
I thank Dr Robert Howard for supervision of thisstudy and
Professor Stephen Jackson and Mr PaulBaskerville for allowing me to
interview patientsunder their care. The study was carried out as
partof a University of London MD thesis.
RAHUL RAODepartment of Old Age Psychiatry, Maudsley Hospital
and Institute of Psychiatry, London
Correspondence to: Dr Rahul Rao, Department ofOld Age
Psychiatry, Guy’s, King’s, and St ThomasMedical School, Job Ward,
Thomas Guy House,Guy’s Hospital, St Thomas Street, London SE19RT,
UK email [email protected]
1 Rao R, Jackson S, Howard R. Primitive reflexesin
cerebrovascular disease: a community studyof older people with
stroke and carotid stenosis.International Journal of Geriatric
Psychiatry (inpress).
2 Burns A, Jacoby R, Levy R. Neurological signsin Alzheimer’s
disease. Age Ageing 1991;20:45–51.
3 Vreeling FW, Houx PJ, Jolles J, et al. Primitivereflexes in
Alzheimer’s disease and vasculardementia. Journal of Geriatric
Psychiatry andNeurology 1995;8:111–17.
4 Alexandrova NA, Gibson WC, Norris JW, et al.Carotid artery
stenosis in peripheral vasculardisease. J Vasc Surg
1996;23:645–9.
5 Phillips NA, Mate-Kole CC, Kirby RL. Neuro-psychological
function in peripheral vasculardisease amputee patients. Arch Phys
Med Reha-bil 1993;74:1309–14.
6 Phillips NA, Mate-Kole C. Cognitive deficits inperipheral
vascular disease. A comparison ofmild stroke patients and normal
controlsubjects. Stroke 1997;28:777–84.
Factitious clock drawing andconstructional apraxia
A 45 year old man presented with a 1 dayhistory of headache,
possible seizures, andleft sided weakness. On the day of
presenta-tion the patient’s wife had twice found him,inexplicably,
on the floor. After the secondsuch episode she brought him to
hospital forevaluation. Examination disclosed a com-plete left
hemiplegia and hemianaesthesia,although muscle tone was documented
to benormal and the plantar responses downgoingbilaterally. Brain
CT was normal and routineblood examination was unremarkable.
Therewere no further seizure-like episodes andthe patient was
transferred to this hospital10 days later, hemiplegia unchanged,
forpossible angiography and further investiga-tions.
He was an exsmoker with hypercholestero-laemia and peripheral
vascular disease whichhad been treated by a left femoral
angioplasty
5 years earlier. The angioplasty was compli-cated by the
occurrence of a seizure, thoughtto be related to dye injection, and
phenytoinhad been prescribed for a short time thereaf-ter. There
was a remote history of heavy alco-hol use, but he had been
abstinent for severalyears. His father had had a stroke at the age
of65.
Six months earlier the patient had also col-lapsed at home and
been taken to hospitalwith a left hemiplegia. Brain CT at that
timewas normal, as were carotid Doppler studiesand an
echocardiogram. During that admis-sion to hospital, several
generalised seizure-like episodes were seen, some with
retainedconsciousness, and he had again been startedon phenytoin
therapy. A follow up outpatientbrain MRI was normal and it was
concludedthat the hemiplegia was non-organic inorigin. He was
described to have made agradual, near complete, recovery from
thisfirst hemiplegic episode and was scheduledfor an imminent
return to work at the time ofhis relapse.
On transfer to this hospital the patient wasalert, oriented, and
cooperative. Although upto date on current aVairs and able to
describethe investigations performed at the transfer-ring hospital,
he scored only 23/30 on a minimental state examination, with absent
threeword recall, impaired registration, and poorcopying of a two
dimensional line drawing.Further bedside neuropsychological
testingshowed other findings indicative of construc-tional apraxia
and left hemineglect. Specifi-cally, when asked to draw a clock
with thetime at 10 minutes to 2 o’clock, all the num-bers, and the
clockhands, were placed on theright hand side of the clock outline
(figure A).Copying of three dimensional line drawingswas also
significantly impaired (figure B).When asked to bisect a line,
however, thepatient did so only minimally to the right ofthe
midpoint (58% of the distance from theleft side).
Cranial nerve examination suggested anincongruent and
inconsistent left hemianop-sia to confrontation testing but was
otherwisenormal, including bilaterally symmetric op-tokinetic
nystagmus. Motor examinationshowed paralysis of the left arm and
leg, withbilaterally symmetric bulk, tone, and deeptendon reflexes.
The plantar response wasflexor bilaterally. Sensory
examinationshowed decreased pinprick and absent lighttouch, joint
position sense, and vibrationsense on the entire left side. There
was alsoimpaired perception of a tuning fork’svibration on the left
side of the forehead, witha distinct demarcation in the midline.
Therest of the physical examination was unre-markable.
Brain CT and MRI, CSF examination, androutine EEG were normal.
Routine haemato-logical and metabolic analyses plus erythro-cyte
sedimentation rate, serum lactate, pro-thrombin time/partial
thromboplastin time,fasting serum glucose, HbA1c, serum Ig sur-vey,
and thyroid stimulating hormone were allwithin normal limits. A
hypercoagulabilityprofile was negative. A lipid profile showedmild
hyperlipidaemia with increased low
Table 1 Primitive reflexes in patients with peripheral vascular
disease (n=25) and controls (n=25)
Hand grasp Foot grasp Glabellar Palmomental Paratonia Rooting
Snout Sucking (tactile) Sucking (visual)
U 274.0 312.5 199.5 287.5 287.0 235.5 287.5 261.0 287.5pValue
0.15 1.0 0.001* 0.15 0.29 0.01* 0.44 0.08 0.30
*Higher mean score in people with peripheral vascular
disease.
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density lipoprotein (3.92 mmol/l) and triglyc-erides (4.30
mmol/l) and low high densitylipoprotein (0.73 mmol/l). Serum
phenytoinconcentration was therapeutic at 74 µmol/l.An ECG was
normal.
Ophthalmological consultation and formalvisual field testing
demonstrated a concentri-cally constricted field of mild degree in
theright eye and tunnel vision in the left eye.
The patient consented to overnight video-EEG monitoring and was
seen on multipleoccasions to move his left arm and/or leg in
anormal fashion, at one point using the leftarm to readjust his bed
covers shortly afterarousal from sleep, before glancing briefly
atthe video camera and completing the taskwith his right arm. The
prolonged EEG wasnormal.
A formal neuropsychological assessmentperformed in hospital
documented impairedattention, concentration, and workingmemory, as
well as several atypical calcula-tion and spelling errors, the
second involvingunusual “near miss” letter substitutions
orreversals (for example, “anixety”, “excecu-tive”). The formal
testing identified noconsistent evidence of visuospatial deficits
orconstructional apraxia. The findings wereinterpreted as
inconsistent with the patient’shistory but the possibility of a
factitious aeti-ology was not specifically addressed—that is,tests
designed to detect malingering duringneuropsychological testing1 2
were not admin-istered by the examiner, who had not beeninformed at
the time of consultation of thepresumptive neurological diagnosis
of malin-gering or factitious disorder.
No further investigations were performedand the patient was
transferred via the origi-nal hospital to a rehabilitation facility
andsubsequently discharged to home. Con-fronted with the findings
of the videomonitoring the patient appeared sanguineand accepting
of the evidence that he shouldbe able to move his left side. Six
months laterhe was ambulatory but otherwise not signifi-cantly
improved. He had been assessed by apsychiatrist but had refused
psychiatric fol-low up, electing instead to be followed up bya
psychologist. He understood his diagnosisto be “conversion
disorder” and reported thathe was actively collecting information
on thesubject via the internet.
Outpatient brain SPECT and visual andsomatosensory evoked
potentials performed1 year after discharge demonstrated no
hemi-spheric abnormalities. The patient remained
oV work and was receiving disability funding.He walked with a
limp favouring his left sideand complained of persistent
decreasedsensation on the left side. Forced choice sen-sory testing
of finger and arm movement onthe left3 demonstrated performance to
beworse than chance (68% wrong choices).Motor bulk, tone, and
reflexes were symmet-ric and plantar responses downgoing. Hedrew a
clock normally at the 1 year follow up.
The clinical and laboratory findings de-scribed above indicate
beyond any doubt thenon-organic nature of this patient’s
lefthemiplegia/hemianaesthesia. His seizure-likeepisodes at
presentation are presumed tohave been non-epileptic in origin (as
hadbeen suspected during his previous admissionto hospital)
although this cannot be defini-tively proved.
The inability to copy line drawings or todraw a clock is, from a
neurologist’s perspec-tive, typically associated with parietal
lobedysfunction, usually of the non-dominanthemisphere, especially
if associated with lefthemispatial neglect.4 To our knowledge,
thisis the first reported case of factitious clockdrawing and
constructional apraxia. Bedsidemental status testing also
demonstrated themore common simulated deficits of impairedattention
and absent three word recall.1 Inretrospect, the severe neglect on
clockdrawing was perhaps “too good to be true”,especially in the
light of the near normal linebisection demonstrated on the same
day. Themirror image distortion of the house was alsovery unusual
and, furthermore, the mirrorreversal itself is evidence of lack of
clinicalneglect. The distortion of the cube, however,could easily
be misinterpreted as evidence oforganic constructional impairment
if seen inthe absence of the other relevent clinical andlaboratory
information.
During follow up, the patient admitted tofeeling tremendous
occupation relatedstresses, and described how he had come toboth
fear and detest his job. Given the clearbenefit to the patient of
removal from hiswork environment, the relapse of his
symp-tomatology just as he was scheduled forreturn to work after
his first non-organichemiplegic episode, and the
intentionalityrequired to feign poor clock drawing
andconstructional apraxia, there is much to sup-port a diagnosis of
malingering.5
Nevertheless, classification as a factitious dis-order is at
least as justifiable in view of the
patient’s willingness to undergo medicalinvestigations,
including video monitoring.
It is unclear how or when the patientacquired the information
needed to mimic aconstructional apraxia. Previous
bedsideneuropsychological evaluations may haveserved to familiarise
him with the format ofsuch testing, acting as an impetus to
researchthe issue of stroke and focal brain deficits(which might
also have occurred after hisfather’s stroke), much in the same way
he isnow researching conversion disorder, therebydiscovering what
expected answers shouldlook like. Despite repeated questioning,
how-ever, no evidence could be gathered from thepatient to support
this speculation.
I KHANI FAYAZ
Division of Neurology
J RIDGLEYDivision of Neuropsychology
R WENNBERGDepartment of Medicine, Division of Neurology,
TheToronto Hospital, University of Toronto, Toronto, ON,
Canada
Correspondence to: Dr R Wennberg, EC8–022,The Toronto Hospital,
399 Bathurst Street, To-ronto, Ontario, Canada M5T 2S8. Telephone
001416 603 5402; fax 001 416 603 5768.
1 Bernard L, Houston W, Natoli L. Malingeringon
neuropsychological memory tests: potentialobjective indicators. J
Clin Psychol 1993;49:45–53.
2 Prigatano G, Amin K. Digit memory test:unequivocal cerebral
dysfunction and sus-pected malingering. J Clin Exp
Neuropsychol1993;15:537–46.
3 Pankratz L, Binder L, Wilcox L. Evaluation ofan exaggerated
somatosensory deficit withsymptom validity testing. Arch Neurol
1987;44:798.
4 Strub R, Black W. Constructional ability. In:Strub R, Black W.
The mental status examinationin neurology. Philadelphia: FA Davis,
1985:101–23.
5 American Psychiatric Association. Diagnosticand statistical
manual of mental disorders. 4th ed,revised. Washington: American
PsychiatricAssociation, 1994.
Anosognosia and mania associated withright thalamic
haemorrhage
Both anosognosia and secondary mania areassociated with right
hemispheric lesions.These two non-dominant syndromes, how-ever, are
rarely described as occurringtogether. We present a patient with a
rightthalamic haemorrhage giving rise to pro-found denial of
hemiplegia and elated mood.This case suggests mechanisms for
thecommon production of mania and anosogno-sia.
A 53 year old, right handed, black man,with a history of alcohol
misuse and depend-ence and untreated hypertension, wasbrought to
the emergency room a few hoursafter developing an intense headache
and leftsided numbness and weakness.
On admission he was described as “bellig-erent,” “agitated,” and
“confused.” Bloodpressure was 240/160. Neurological exam-ination
disclosed left lower facial droop,decreased left corneal and gag
reflexes, andleft hemiparesis with dense sensory deficits.With
increasing obtundation, the patient wastransferred to the intensive
care unit andintubated. Brain MRI showed a large, rightsided,
hyperacute thalamic bleed with masseVect and oedema. The patient
was extu-bated 2 days later and 4 days after the strokehe was
described as being drowsy andinattentive, but was able to answer
questions
(A) Asked to: “put all the numbers on a clock and make the time
ten to two”. (B) Patient’s copies (atright) of three dimensional
line drawings. Top: common constructional distortion of cube.
Bottom:unusual mirror image representation of house.
A B
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appropriately. Neurological examinationshowed contralateral gaze
preference, supra-nuclear vertical gaze palsy, diYculty
converg-ing, left sided flaccid hemiparesis, and dense,left sided
hemianaesthesia. Deep tendonreflexes were absent on the left and
Babinski’sreflex was present on the left. In addition,visual
extinction and neglect were present.
At the time of onset of right sided weaknessthe patient insisted
that he was “fine,” and anambulance was called over his
objections.After being extubated, the patient acknowl-edged that he
had had a stroke, but, despitehis hemiparesis, insisted that he was
ready togo home and go back to work. His belief in hisability to
walk led to near falls, and he wasmoved to a room nearer to the
nurses’ stationfor closer observation. He told the nurses
thatsomeone else’s arm was in his bed. On oneoccasion, holding up
his left arm with hisright, he told the nurse to, “take it away;
itkeeps scratching me.” That the left arm“smelled funny” was
another reason hewanted the nurses to take it away.
Four weeks after the stroke he firstacknowledged that his left
arm belonged tohim. He spontaneously recalled believingotherwise.
By this time he had a moderatehemiplegia and recognised “a little
weak-ness,” but continued to insist that he was welland able to
return to work. By the 6th weekafter stroke the patient more
consistentlyacknowledged that he was weak on the leftside of his
body. A request for disabled hous-ing “so that I won’t be a burden
to my family”seemed to indicate an appreciation of hisimpairment,
but this insight was fleeting;within an hour of making such
statements thepatient might insist that after a week’sexercise he
would be ready to return to work.His awareness of his hemiplegia
fluctuatedfor 8 weeks after stroke before becomingfixed, but
remained shallow after 12 weeks; heno longer planned to return to
work andapplied for social security disability insurance“because
they say I’m disabled.”
The patient’s mood was remarkably cheer-ful and optimistic. A
week after the stroke hewas noted to praise extravagantly the
hospitalfood, and the nurses found him “talkative.”When he arrived
on our ward 11 days afterthe stroke he was flirtatious with female
staVand boasted of having fathered 64 children.His girlfriend was
surprised when he kissedher in front of the staV because he had
neverpublicly displayed aVection before. He re-ported excellent
energy and expansivelyinvited all of the staV to his home for
thanks-giving. Sleep was not disrupted or reducedand he had a good
appetite. When beginningto acknowledge his left sided weakness,
heremained blissfully unconcerned. He scored31 points on a mania
rating scale,1 which waswell in the manic range. The mania
resolvedgradually over a 10 week period after stroke.
Other than alcoholism, the patient had nohistory of psychiatric
illness and there was nofamily history of psychiatric illness.
Thepatient had not seen an physician in manyyears. Visual acuity
was found to be reducedto 20/800 in both eyes on the basis of
hyper-tensive retinopathy.
Evaluation 1 month after stroke showedmany deficits and a few
strengths. Inattentionto the left hemispace was marked. By 2months
after stroke he no longer extinguishedto double simultaneous
stimulation, but,although he could see to the left, was
stillmissing targets in his left visual hemifield.Visual
integration, both with and without therequirement of construction,
was severely
impaired. He was able to correctly recogniseand produce facial
emotional information.Simple attention was intact, but
attentionalcontrol (backward span and mental control)was impaired.
Visuomotor tracking was slowand he had significant problems with
concep-tual shifting (both auditory and visual). Lan-guage
processing diYculties included verypoor reading ability, impaired
confrontationnaming, and impaired performance on a ver-bal task of
fluency and initiation. Auditorycomprehension was mildly impaired.
Vo-cabulary scored formally in the borderlineimpaired range, as did
abstract verbal reason-ing. On tests of praxis he demonstrated a
ten-dency to use the hand as object. Memoryperformances were
relatively intact. Hisinitial recall of two paragraphs scored
for-mally within the low average range and after a30 minute delay,
he was able to recall most ofthe information initially encoded,
scoringformally within the average range.
Structural brain MRI on admission to theemergency room showed a
large right tha-lamic hemorrhage with mass eVect andoedema, with
oedema extending into the cer-ebral peduncle with internal
susceptibilityconsistent with deoxyhaemoglobin. Alsopresent was
increased T2 signal bilaterally infrontal areas consistent with
ischaemicchanges. Brain CT 30 days after strokeshowed, in addition
to the thalamic lesion,moderate cerebellar atrophy and mild
tomoderate prominence of the frontal corticalsulci compatible with
cerebral atrophy.
Structural MRI performed 44 days afterthe stroke showed a 2 cm
right thalamic hae-matoma. Functional MRI2 performed thesame day
demonstrated a 2 cm area of absentcerebral blood volume at the
posteriormargin of the right thalamus without any evi-dence of
decreased cerebral blood volumewithin the right parietal, frontal,
or temporalcortex.
This is a case of anosognosia of hemiplegiaand mania
co-occurring in a patient with alarge right thalamic haemorrhage.
Althoughanosognosia and mania are not generallythought of as
occurring together, whenBabinski3 introduced the term anosognosiahe
used as one of his examples a case in whichthe patient, though not
confused, was “a littleoverexcited,” and in a later paper he
pre-sented a case4 in which there was “a certainagitation, which
expresses itself by exagger-ated loquacity, a decrease in
attention, and atendency to erotic ideas.” Weinstein andKahn5 noted
that euphoria was common inpatients with anosognosia. Moreover,
al-though Cutting6 emphasised that apathy isthe mood more usually
associated withanosognosia, 10% of his patients with ano-sognosia
were described as having “euphoricmood.”
Right sided thalamic lesions are known toproduce both
anosognosia and mania, but therelation of each to the pathology is
unclear.Only some of the patients with right hemi-spheric lesions
are manic or agnosic. Thesetwo syndromes may be related to
dysfunctionof diVerent neural networks and only occurtogether when
a disease process aVects bothnetworks.
Another possibility is that these syndromesare aetiologically
related. Could anosognosiabe a manifestation of mania? Although it
iseasy to conceive how elevated mood mightfacilitate anosognosia of
hemiplegia (or othertypes of anosognosia), it is diYcult to
explainthe presence of denial of ownership anddislike of the left
arm (other anosognosic
phenomena) on the basis of euphoria.Moreover, Starkstein et al,7
finding that simi-lar frequencies and severities of major andminor
depression were present in patientswith and without anosognosia,
suggest that aparticular mood state may not necessarilyinfluence
insight.
Several explanations have been proposedto explain the phenomenon
of anosognosia.8 9
All the models invoke dysfunction of the cer-ebral cortex,
especially the parietal cortex. Itis interesting that in this case
functional MRIfailed to demonstrate decreased CBV in theparietal
lobe.
In summary, we present a case of maniaaccompanying anosognosia
in a patient with aright thalamic haemorrhage. The coexistenceof
mania and anosognosia may be more com-mon than previously
appreciated. The associ-ation with anosognosia implies that
themechanisms implicated in the pathogenesisof secondary mania may
be similar to those ofanosognosia. The absence of evidence
ofabnormal parietal, temporal, or frontal lobefunction by
functional MRI in this case isintriguing.
ELIZABETH LIEBSONDepartment of Psychiatry, Tufts, New
England
Medical Center, 750 Washington Street, Box 1007,Boston, MA
02111, USA. Telephone 001 617 636
1633; email [email protected]
1 Bech P, Kastrup M, Rafaelsen OJ. Mini-compendium of rating
scales for states of anxi-ety, depression, mania, schizophrenia,
withcorresponding DSM-III syndromes: maniascale. Acta Psychiatr
Scand 1986;73(suppl236):29–31.
2 Belliveau J. Functional cerebral imaging by sus-ceptibility
contrast NMR. Magn Reson Med1990;14:538–546.
3 Babinski J. Contribution a l’etude des troublesmentaux dans
l’hemeplegie organique cereb-rale. Rev Neurol 1914;22:845–8.
4 Joltrain E. Un nouveau cas d’anosognosie. RevNeurol
1924:638–40.
5 Weinstein EA, Kahn RL. The syndrome of ano-sognosia. Arch
Neurol Psychiatry 1950;64:772–91.
6 Cutting J. Study of anosognosia. J Neurol Neuro-surg
Psychiatry 1978;41:548–55.
7 Starkstein SE, FedoroV JP, Price TR, et al. Ano-sognosia in
patients with cerebrovascularlesions: a study of causative factors.
Stroke1992;23:1446–53.
8 Ellis SJ, Small M. Denial of illness in stroke.Stroke
1993;24:757–9.
9 Heilman KM. Anosognosia: possible neuro-psychological
mechanisms. In: Prigatano GP,Schacter DL, eds. Awareness of deficit
after braininjury. New York: Oxford University
Press,1991:53–62.
Epileptic cardiac asystole
A patient is reported on with habitualepisodes of collapse and
loss of consciousnessassociated with EEG evidence of
focalepileptiform discharges. Simultaneous ECGrecordings disclosed
25 seconds of cardiacventricular asystole occurring 24 secondsafter
the onset of electrical seizure activity.After changes to
antiepileptic medication andthe insertion of a permanent cardiac
pace-maker he has had no further episodes. Incases of epileptic
cardiac dysrhythmia, iso-lated EEG or ECG recording may
proveinsuYcient and prolonged simultaneousEEG/ECG monitoring may be
required.
Cardiac arrhythmias subsequent to epilep-tic seizures have been
recognised for morethan 90 years. They provoke diagnosticconfusion
and may be a mechanism ofsudden unexplained death in
epilepsy.Whereas sinus tachycardia was noted toaccompany more than
90% of epilepticseizures, isolated bradycardia was seen much
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less commonly (only 1 of 74 seizuresrecorded).1 A review in 1996
of the “ictalbradycardia syndrome” showed only 15documented cases
in the literature of eitherbradycardia or asystole associated
withseizures.2 Most patients had temporal lobeseizures. The longest
duration of asystolepreviously reported is in a 17 year old manwith
temporal lobe epilepsy who sustained a22 second pause in cardiac
output. More
typically the asystolic periods in documentedcases are in the
region of 5–10 seconds.2
Shorter duration asystole may not compro-mise cerebral function
suYciently to causeloss of consciousness. Implantation of acardiac
pacemaker is advocated but does notensure that lapses of
consciousness are elimi-nated if these are directly related to
theseizure rather than to the secondary asystole.We report on a
patient with epileptic cardiac
asystole of 25 seconds duration demonstratedby prolonged
simultaneous EEG/ECG moni-toring which responded well to
pacemakerinsertion.
A previously well 34 year old right handedbuilder was referred
with a 1 year history offortnightly episodes of loss of
consciousness.There was no associated warning, aura, chestpain, or
palpitations and the patient was onlyaware of the episode once
consciousness was
16 Channel ictal EEG (eight channels illustrated with ECG)
showing electrographic seizure onset and subsequent bradycardia and
asystole.
Gain
Paper speed : 1.34 cm/s
Filter setting : Lf : 35 Hz
3
4
T5 T6
2
1
A
F8-T4
T4-T6
F7-T3
T3-T5
T4-C4
C4-Cz
Cz-C3
C3-T3
EKG
Time : 07:04:34
BF8-T4
T4-T6
F7-T3
T3-T5
T4-C4
C4-Cz
Cz-C3
C3-T3
EKG
Time : 07:04:58
C
F8-T4
T4-T6
F7-T3
T3-T5
T4-C4
C4-Cz
Cz-C3
C3-T3
EKG
Time : 07:05:21
T4C4CZC3T3
8 7 6 5
F8F7
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restored and he found himself lying on thefloor. On recovery
there was no confusion,drowsiness, dysphasia, or diuresis.
Often,however, he sustained soft tissue injuries tohis face and
scalp.
Witnesses reported that the patient would,without warning,
suddenly collapse to theground where he would remain
unrousable,inaccessible, and motionless for 90 to 120seconds. On
two occasions he appeared con-fused and disorientated immediately
before acollapse. During the period of unconscious-ness he would
demonstrate no involuntarymovements, orofacial automatisms, or
cyano-sis but he would become pale and “ashen”while staring
straight ahead with a glazedlook. On resolution of the episode his
colourwould return to normal and within 2 minuteshe would have
fully recovered. Unusuallyduring one reported episode of
unconscious-ness he was seen to briefly extend the fingersof both
hands.
He was admitted to his local hospital andCT, MRI, interictal
EEG, and 24 hour ECGwere normal. No episodes were witnessedwhile he
was an inpatient but they werethought to be epileptic in origin and
thereforehe was started on phenytoin, with no benefit.Carbamazepine
was added, again with mini-mal eVect.
The patient was then referred to theEpilepsy Assessment Centre
of The NationalSociety for Epilepsy and National Hospitalfor
Neurology and Neurosurgery for furtherinvestigation and
management.
Cardiovascular and neurological examina-tion was normal, as were
MRI and routineinterictal EEG. Sixteen channel ambulatoryEEG using
an Oxford Instruments digitalEEG receiver was performed
continuously for340 hours before an episode was
captured.Interictally rare spikes were seen over the
rightfrontocentrotemporal region during sleep. Theonset of the
episode was not witnessed and thepatient was found lying on the
floor, regainingconsciousness at about 07:06. The event EEGshowed a
short run of bilateral semirhythmic2–3 Hz activity at 07:04:34
(figure A), persist-ing for 8 seconds before being obscured
bymuscle and movement artefact. Twenty fourseconds after the first
EEG change, at07:04:58, the ECG changed from sinusrhythm at 90 bpm
to a brief period of sinusbradycardia, followed by a period of
asystolewith only very occasional ventricular com-plexes lasting
25–30 seconds (figure B). After afew seconds of bradycardia then
tachycardia,sinus rhythm was restored. Throughout theepisode the QT
interval on the ECG remainedwithin normal limits. The EEG became
visibleagain 16 seconds into the asystolic period, atwhich time it
was dominated by diVuse lowamplitude slow activity at 41)) nerves.
There weremoderate decreases in the amplitude of com-pound action
potentials in all the nervestested, and an amplitude reduction of
50%was detected across the cubital tunnel of theright ulnar nerve.
Minimum F wave latencieswere prolonged in all the nerves tested.
Thelatency in the right phrenic nerve was slightly
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delayed (8.7 ms (normal
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venous thrombosis is often asymptomatic, orpresents with
non-specific pain, it is probablyunrecognised in many cases.2
Concurrentipsilateral spinal accessory neuropathy andinternal
jugular venous thrombosis after CEAis expected to be rare, and this
is underscoredby the lack of published cases. Despite thisapparent
rarity, a common pathogeneticmechanism for postoperative spinal
accessoryneuropathy and internal jugular venousthrombosis may well
be present, at least insome cases, which may lead to the
considera-tion of the possibility of both when either
isdiscovered.
We report on a patient who developed rightspinal accessory
neuropathy and internaljugular venous thrombosis after right
CEA.
A 59 year old man underwent right CEAfor possibly symptomatic
stenosis. Angio-graphy had shown 90% stenosis of the rightinternal
carotid. The operation was doneunder general anaesthesia. The
carotid bifur-cation was unusually distal, necessitating along
dissection and high retraction. Noimmediate postoperative
complications wereevident. The next day, the patient complainedof
mild pain at the operative site, but he didnot notice any weakness.
The pain spreadinto his right shoulder within several days; atthat
time, he also noted diYculty raising hisright arm. His symptoms
worsened further afew weeks later. The symptoms persisted, andhe
presented for neurological evaluation 4months after CEA. At that
time, he had someinduration along the incision site and apalpable
cord within the right supraclavicularfossa. There was moderate
atrophy of theright sternocleidomastoid and trapezius, withright
shoulder drooping and minor rightscapular winging. Right arm
abduction pro-duced more prominent scapular winging andwas limited
to 90 degrees due to pain andweakness. Electrodiagnostic studies
wereconsistent with partial right accessory neu-ropathy with minor
denervation of the righttrapezius. Cervical ultrasonography and
MRIdemonstrated right internal jugular venousthrombosis. The
patient was treated with ashoulder support, analgesics, and low
doseaspirin. There was no significant clinicalchange 1 year after
CEA. Repeat electrodiag-nostic studies were consistent with
severechronic right spinal accessory neuropathy,and repeat
ultrasonography showed persist-ent right internal jugular venous
thrombosis.
Spinal accessory neuropathy was firstreported as a complication
of CEA in 1982.3
Since then, there have been several casereports and small
series.1 4 A 1996 review ofreports of cranial neuropathy after
CEAdisclosed only one patient with spinal acces-sory neuropathy in
over 3000 cases.1 Al-though the authors did not include
severalother reports3 4 which, taken together, mayseem to suggest a
somewhat higher incidence,the overall small number of reported
cases inproportion to the hundreds of thousands ofCEAs that have
been done worldwidesuggests that clinically significant
spinalaccessory neuropathy is a rare complication.Minor or
transient spinal accessory neu-ropathy after CEA may be more
frequent.The cause of spinal accessory neuropathyafter CEA is
usually not well established, butintraoperative nerve stretching or
compres-sion from retraction is most often invoked.4
Delayed onset (after 3 weeks) has been notedin some; for these
patients, postoperativeinflammation and scarring seem more
likelycauses. Spinal accessory nerve transection
orischaemia/infarction (arterial or venous) are
other possibilities. As in our patient, highcarotid dissection
and retraction have beenreported to precede spinal
accessoryneuropathy.1 4
The spinal accessory nerve courses alongthe internal jugular
vein and near the internalcarotid artery, typically well above the
carotidbifurcation. It stands to reason that a highincision and
retraction resulting from a highcarotid bifurcation would place the
nerve atrisk. Whether this realisation may lead to anytechnical
modification to decrease the risk ofspinal accessory neuropathy in
those with ahigh bifurcation is unclear.
From our search, internal jugular venousthrombosis after CEA has
been reported inonly one case.2 As Southcott et al noted,retraction
of the internal jugular during CEAmay cause complete occlusion,
leading tothrombosis from venous stasis or endothelialinjury. Other
causes of internal jugularvenous thrombosis include jugular
cannula-tion, blunt cervical trauma, and a hyperco-agulable state.
Internal jugular venous throm-bosis may occur within a week after
neckdissection, often with recanalisation after sev-eral
months.5
The presence of induration about the inci-sion site and a
palpable supraclavicular cordin our patient led us to suspect
venousthrombosis. Internal jugular venous throm-bosis may often be
asymptomatic. Potentialsymptoms of internal jugular venous
throm-bosis include headache