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!