+ The neuropsychiatry of MS, white matter disorders and autoimmune encephalopathies. John O’Donovan.

+

The neuropsychiatry of MS, white matter disorders and autoimmune encephalopathies. John O’Donovan.

+Multiple Sclerosis: epidemiology

85,000 patients with MS in UK

Prevalence is 100-150/100,000

Incidence is 3.5-7.5/100,000

Plymouth 250,000 total population=perhaps up to 400 patients.

2:1 female to male ratio

Onset between 20-40 years of age

+MS basics: risk versus latitude

+Aetiology

Autoimmune illness link

Genes 30% concordance ID versus 5% in dizygotes

Hygiene hypothesis?

Infections in particular EBV 99% prior infection in MS rather then 90% non affected.

Vit D-high levels are protective, sunlight?/latitude

Smoking modest risk factor

+Pathophysiology

Genetics+environmental agent = relapse

T cells activated, cross BBB, cause inflamatory cascade in white matter which causes acute and chronic lesions. Increasingly apparent, that there is also axonal damage and grey matter damage and damage in NAWM (normal appearing white matter)

Ultimately results in loss of myelin which leads to problems with saltatory conduction, axonal loss which is a later stage and wide spread disease within the brain and spinal cord.

+Clinical types

Relapsing remitting 85% of MS as a rule of thumb: 1relapse per year.

Secondary progressive 40% at ten years and 80% at twenty years

Primary progressive 10-15% of MS, equal male:female ratio

+Clinical features

Frequently presents with optic neuritis

Spinal cord: transverse myelitis

Chronic spasticity

Cerebellar syndrome

Spastic paraparesis

Soft sensory signs

Very varied.

+Diagnosis

Clinical history of lesions disseminated in time and space.

MRI

CSF

VER/BAERs

+MRI of ms brain.

+Treatments

Steroids

Immunosurpression

Beta interferons associated with flu and depression

Glatiramer acetate:aa compound,reduce immune response

Mitoxantrone; antineoplastic

Natalizumab;monoclonal antibody

+Psychiatric features

Dementia

Prevalence of dementia estimated at 10%

Correlates with volume of white matter damage, 30cm squared or above

Occurs in well established disease

Fluctuates with infection, other factors that influence white matter conduction.

+Psychiatric features 2

Depression

Prevalence is 50% plus

Similar to stroke, biological and psychological reactions

Responds to SSRIs

+Psychiatric features 3

Mania/BPAD

Increased prevalence of BPAD

Manic features

Distinction between emotional lability and mania may be difficult

Mood stabilisers, valproate.

+Other white matter disorders which may present to psychiatrists Inflamatory: MS, vasculitis SLE, sarcoidosis, Bechet’s

Vascular disease: small vessel disease, Antiphospholipid, CADASIL

Infectious: PML,HIV, Lyme, Whipple’s, Syphilis

Metabolic: CPM, B12 deficiency

Leucodystrophies: adrenoleucodystrophy, metachromatic leucodystrophy, vanishing white matter disease

Other: mitochondrial,tumour

+Basics

White matter disorders have a different presentation

Remember no cortical signs

Concept of sub cortical dementias

Slowness, spasticity, disconnection,

Emotional lability

Depression

Apathetic and slow

+Likely and unlikely causes of white matter abnormality on a scan Vascular

MS

Everything else is exceedingly rare and there should be clinical evidence to focus the mind.

Inflalamatory, infectious evidence

Leucodystrophies and other unusual white matter disorders are very rare in adult life, unlikely to be seen by any psychiatrist unless working in a specialist centre.

+Conclusion about white matter disorders

Cognitive disorders and depression are common in all

MS is undoubtedly the commonest and will be seen by all psychiatrists who have a busy practice

Depression is common in MS

Some treatments such as beta interferons are associated with depression

Other white matter disorders are uncommon, in general white matter abnormalities on MRI scans tend to be vascular or demyelinating

+Alexia without agraphia

Left occipital stroke and splenium

Visual info is bilateral

However from left occipital must access right visual identification area

Alexia with agraphia orignally described by Djerine

+Conduction dysphasia

Dissconnect between Broca’s and Wernicke’s

Repetition impaired

Another dissconnection

+Schizophrenia?

DTI white matter tracts

Suggestion that disordered connections underlie much of the damage.

+The autoimmune encephalopathies

Unusual collection of illnesses coming to prominence in the last ten years or so and now becoming main stream.

They are beginning to seep into the psychiatric literature.

In essence, common themes, relative absence of structural imaging changes, pathological autoantibodies or inflamatory responses and a clinical triad of cognitive disturbance, psychiatric disturbance and seizures.

They are uncommon and normally present to neurologists as atypical dementias, prolonged unusual deliriums or unusual epilepsies. Suspicion that they are also presenting to psychiatrists and being missed.

+Autoimmune encephalopathies 2

Hashimoto’s encephalopathy/steroid responsive encephalopathy, high titre of antithyroid antibodies, confusion, seizures and psychiatric prolblems .

Voltage gated K channel autoantibody-similar presentation, two types one is paraneoplastic and one is not. About 1/3 is paraneoplastic, 2/3 are not, good prognosis with treatment. Frequently associated with psychiatric features.

Limbic encephalitis secondary to neoplasia, associated with breast, ovarian, testicular cancers and specific autoantibodies such as anti Hu and anti Yo, sometimes also associated with cerebellar disease and or posterior column problems .