Paraneoplastic neurological syndromes: clinical expression Dr Jan Novy Médecin associé, PD & MER Service de neurologie Département des neurosciences cliniques
Paraneoplastic neurological syndromes: clinical expression
Dr Jan Novy
Médecin associé, PD & MER
Service de neurologie
Département des neurosciences cliniques
Plan
• General aspects
• Main symptoms• Confusion/seizures/jerks
• Weakness/numbness
• Incoordination
• Stiffness/pain
• Conclusions
Anti-NMDA encephalitis
Cerebellar degeneration
Limbic encephalitis
Opsoclonus - myoclonus
Stiff person syndrome / PERMSensitive neuronopathy(Dennis-Brown)
Polymyosite / dermatomyositis
Lambert-Eaton syndromeMyasthenia gravisNeuromyotonia
Axonal polyneuropathyInflammatory demyelinating neuropathy
Autonomic neuropathy
General features
• Uncommon (<1% of cancer?)
• Auto-immune +/- paraneoplastic
• Subacute onset (weeks- month(s))
• Majority (60%) precedes the tumour discovery
• Severe course, requires early diagnosis and treatment
• At times, infection (HSV) precedes the symptoms
Armangue et al. Ann Neurol 2014
General features
• Classical syndromes, but overlaps possible
• Small cell lung cancer (neuroblastoma in children) most common provider
• Anti-PD1 therapy is a new provider
• Some(anti-NMDA encephalitis, myasthenia gravis) associated withspecific auto-antibodies: antibody is effector
• For most syndromes, autoantibody are little specific (more specific of a tumour): antibody is not the effector
Symptoms
• Confusion/seizures/jerks
• Weakness/numbness
• Incoordination
• Stiffness/pain
• dysautonomia
Symptoms
• Confusion/seizures/jerks• Limbic encephalities
• Anti-NMDA encephalitis
• Opsoclonus myoclonus
• Weakness/numbness
• Incoordination
• Stiffness/pain
• dysautonomia
Symptoms
• Confusion/seizures/jerks
• Weakness/numbness• Axonal polyneuropathy/Inflammatory demyelinating neuropathy
• Myasthenia gravis
• Lamberton Eaton syndrome
• Polymyositis and dermatomyositis
• Incoordination
• Stiffness/pain
• dysautonomia
Symptoms
• Confusion/seizures/jerks
• Weakness/numbness
• Incoordination• Cerebellar degeneration
• Sensory neuronopathy (ganglionopathy)
• Stiffness/pain
• dysautonomia
Symptoms
• Confusion/seizures/jerks
• Weakness/numbness
• Incoordination
• Stiffness/pain• Stiff person syndrome / Progressive encephalomyelitis with rigidity and
myoclonus (PERM)
• neuromyotonia
• dysautonomia
Symptoms
• Confusion/seizures/jerks
• Weakness/numbness
• Incoordination
• Stiffness/pain
• Dysautonomia• Autonomic neuropathies
• Lambert-Eaton symdrome
Confusions/seizures/jerks
Limbic/anti-NMDA encephalitis
• Psychiatric symptoms > confusion > seizures
• Abnormal movements coma (anti-NMDA)
Vernino S et al.Neurologist 2007;13: 140-7.Gultekin SH et al. Brain 2000: 123; 1481-1494Pittock SJ et al. Ann Neurol 2003: 53; 580-587
Anti-NMDA encephalitis
VIDEO
1
Courtesy of Dr Alvarez, Sion
Confusions/seizures/Jerks
Opsoclonus-myoclonus
• Spared cognition
• Gaze instability, gaze (+/- neck) jerks
• Axial > appendicular jerks
• Ataxia, mostly in gait
• Difficulty swallowing
VIDEOS
2+3
Courtesy of Dr Alvarez, Sion
Micieli et al, Neurology 2019
Incoordination
Cerebellar degeneration
• Gait instability
• Oscillopsia, diplopia
• Doth truncal and appendicular ataxia
• Dysarthria
• Dysphagia
Scheid et al,
JNNP 2006
Incoordination
Sensory neuronopathy (ganglionopathy)
• Neurogenic pain (large fibres)
• paraesthesia
• Proprioceptive ataxia
• pseudo-athetosis
• areflexia
VIDEO
4
Courtesy of Prof. Kuntzer Lausanne
Weakness/numbness
Peripheral neuropathies (axonal or demyelinating)
• Distal numbness, weakness, amyotrophy loss of osteo-tendinous reflexes
• Proximal involvement in demyelinating form
• Other systems involved (skin, endocrine…)
Kutlubay et al, JEADV 2016 Wang et al, Medicine, 2018
Weakness/numbness
Lambert-Eaton syndrome
• Proximal progressive weakness (lower>upper body)
• Constipation, dry mouth
• Orthostatic hypotension
Improvement after maximal exercise (20sec)
Petty A. Pract Neurol 2007; 7: 265–267
Merino-Ramírez et Bolton. Canadian Journal of Neurological Sciences 2016
VIDEO
5
Weakness/numbness
Polymyositis/Dermatomyositis
• Muscle ache (like after strenuous exercise)
• Proximal progressive weakness
• Dysphagia
• Heliotropic skin rash (dermatomyositis)
• Usually mild cardiac involvement
Courtesy of Prof. Kuntzer,
Lausanne
Stiffness/pain
Neuromyotonia
• Continuous muscle twitching
• Muscle stiffness
• Muscle hypertrophy
• Weight loss
• Hyperhidrosis
VIDEO
6
Min Qian et al, JAMA Neurol 2019
Stiffness/pain
Stiffman person syndrome
• Muscle axial stiffness
• Painful muscular spasms
• Lumbar hyperlordosis
• Hyperekplexia/startle
Espay et al. Muscle Nerve 34: 677–690, 2006
Espay et al. Muscle Nerve 34: 677–690, 2006
Courtesy of
Dr Rossel,
CHUV
Conclusions
• Uncommon, but dramatic course
• Subacute onset, tumours most often not known at the time of symptoms
• At times, benign infection preceding
• Wide clinical spectrum, can affect virtually any part of central/peripheral nervous system
Thank you!