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Central nervous system involvement & Neuromuscular

• Toxic
  • Cholinesterase Inhibitors (Organophospates)
  • Hexacarbons: Occasional delayed myelopathy
  • Nitrous oxide (N₂O)
• Hereditary
  • Adrenomyeloneuropathy
  • Adult-onset Leukodystrophy
  • Charlevoix-Saguenay - Spastic Ataxia
  • Familial spastic paraparesis
  • Metachromatic Leukodystrophy
  • SOX10
• Neoplastic: Lymphoma (angiotropic large-cell)
• Cuban neuropathy
• Vernant's disease

• Ataxias
  • Friedreich
  • Mitochondrial - NARP Syndrome: (Neuropathy; Ataxia; Retinitis Pigmentosa)
  • Posterior column ataxia + Retinitis pigmentosa
• Hereditary neuropathy
  • HMSN VI
  • CEDNIK
  • AAA syndrome
• Toxic
  • Alcohol
    
  • Carbon disulfide
  • Chloramphenicol
  • Disulfiram
  • Isoniazid
  • Mercury (Hg)
  • Nitrous oxide (N₂O)
• Nutrition: Cuban neuropathy
• Vernant's disease

• Hereditary Motor-Sensory Neuropathies: HMSN, CMT & Other
  • X-linked
    • Cowchock
    • HMSN X (Connexin 32)
  • Recessive
    • CMT 4D (Lom)
    • Refsum
    • Xeroderma Pigmentosum
    • HMSN & Deafness
    • HMSN, Optic neuropathy & Hearing loss
    • Hereditary ataxia with thermoanalgesia & loss of fungiform papillae
    • CEDNIK
  • Dominant
    • CMT 1A (Ala67Pro mutation in PMP-22)
    • CMT 1B (Thr124Met mutation in P0)
    • CMT 2E
    • Connexin-31 (D66del mutation)
    • HMSN & Deafness
    • HMSN 6
    • Dejerine-Sottas (Dominant)
    • HSN + Cough & GE reflux
• Motor neuron disorders
  • Brown-Vialetto-van Laere
  • Madras
• Muscular dystrophy & Myopathy
  • FSH
  • Scapuloperoneal
  • Myhre syndrome
• Other hereditary disorders
  • Neuralgic Amyotrophy, Hereditary (HNA1)
  • Hirschsprung: HSCR2; SOX 10
  • Sensory neuropathy with scoliosis & deafness (Robinson)
  • Sensory neuropathy, Deafness & Global delay
  • Anhidrotic ectoderma dysplasia
  • Mitochondrial
  • Neurofibromatosis-2
  • Neuroaxonal Dystrophy (Late infantile)
  • Coffin-Lowry
  • Duane's syndrome
  • Dilated cardiomyopathy with sensorineural hearing loss (CMD1J; CMD1K)
• Other acquired disorders
  • Cuban epidemic neuropathy
  • Hypothyroidism
  • Paraneoplastic (Anti-Hu)
  • Sarcoid
  • Superficial siderosis

• Hereditary
  • A-β-lipoproteinemia
  • Adult-onset Leukodystrophy
  • Ataxia with neuropathy
    
  • Ataxia with Oculomotor apraxia (AOA): 1; 2
  • Ataxia telangectasia
  • Ataxia, Tremor & Cognitive decline
  • Cerebrotendinous Xanthomatosis
  • Charlevoix-Saguenay - Spastic Ataxia
  • Friedreich Ataxia
  • Infantile Onset Spinocerebellar Ataxia (IOSCA)
  • Metachromatic Leukodystrophy
  • Pelizaeus Merzbacher-like
  • Refsum
  • RPIA deficiency
  • Salla disease
  • SCA 1, 2, 3, 4
• CANVAS
  
• Paraneoplastic: Hu; CV2
• Alcohol
• Creutzfeld-Jakob

• Hereditary
  • ALS, Familial: Higher prevalence of dementia (~15%) than sporadic ALS
  • CEDNIK
  • Chorea-Acanthocytosis
  • CMT
    • 1X: Transient encephalopathy
    • Andermann: Agenesis of corpus callosum
  • Cowchock Syndrome
  • Fabry's
  • Hexosaminidase A (Late Onset Tay-Sachs)
  • Hypomyelination & Congenital cataract
  • α-Methyl-acyl-CoA-racemase
  • Minifascicles & 46,XY Gonadal dysgenesis
  • Multi-Infarct Dementia (CADASIL)
  • Polyglucosan body syndromes
  • Porphyria
  • Prion protein (PrP27-30) mutation: Glu200Lys
  • Salla disease
  • SOX10
• Infections
  • HIV
  • Lyme disease
  • Rabies
  • Syphilis
• Inflammatory & Immune
  • Sarcoid
  • Vasculitis
• Metabolic
  • Thyroid
  • Vitamin B₁₂ deficiency
  • Hypophosphatemia
• Mitochondrial:
  • MELAS (Mitochondrial Encephalomyopathy; Lactic Acidosis; Stroke)
    
  • MERRF (Myoclonic Epilepsy; Ragged Red Fibers
    
  • MNGIE Syndrome (Myopathy and external ophthalmoplegia; Neuropathy; Gastro-Intestinal; Encephalopathy)
• Motor neuron disorders with dementia (Sporadic)
  • Western Pacific ALS
  • Frontal Dementia followed by motor system disease
    • Upper motor neuron: Especially bulbar
    • Lower motor neuron: Fasciculations; Less prominent weakness
    • ? Atypical Creutzfeld-Jacob syndromes
• Neoplastic: Lymphoma (angiotropic large-cell); Carcinomatous meningitis
• Paraneoplastic: anti-Hu
• Toxic: Alcohol; Anticholinergic; Arsenic; Lead; Mercury; Podophyllin; Thallium; Vacor

• Metachromatic Leukodystrophy
• Krabbe
• Neuroaxonal Dystrophy
• Giant Axonal Neuropathy
• Camera-Marugo-Cohen Syndrome
  

• Leukodystrophy
• Adrenomyeloneuropathy
• Adult-onset
• Cockayne A; B
• Hypomyelinating
  
• HLD1 (Pelizaeus-Merzbacher)
• HLD2
• HLD3
• HLD4
• HLD5
• HLD6
• HLD7 (TACH)
• Krabbe
• L-2 Hydroxyglutaric acidemia
• Maple syrup urine disease
• Metachromatic
• Mitochondrial
• Salla disease
• Spastic paraparesis & Dystonia
• Tay syndrome (Trichothiodystrophy + Congenital ichthyosis)
• Vanishing white matter
• Leukoencephalopathy
  • Ataxia, UMN & Polyneuropathy
  • Brain stem & Spinal cord
  • CADASIL
  • Infantile
  • LBSL

Multi-Infarct Dementia (CADASIL)   l NOTCH 3 ; Chromosome 19q12; Dominant Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Clinical Onset: Adult Ischemic events: Recurrent; Subcortical Migraine Cognitive dysfunction: Dementia; Psychiatric disorders Neuropathy3 Often subclinical Occasional clinical features Sensory loss (40%): Distal; Symmetric Weakness (30%): Distal Areflexia Electrodiagnostic: Axon loss NCV: Mildly slow motor & sensory CMAP & SNAP: Reduced amplitudes MRI Leukoencephalopathy: Especially anterior temporal Subcortical infarcts Pathology Angiopathy (Small arterial vessels) Vessels: Granular deposition of material in smooth muscle layer Staining: Congophilic, PAS positive material in vessel walls Location: Brain; Skin; Muscle; Nerve Peripheral nerve Axon loss: Myelinated axons; Mild to moderate Electron microscopy of peripheral nerve & muscle Electron dense deposits associated with smooth muscle cells (vascular)

from R Schmidt MD CADASIL Vessels in brain

Chorea-Acanthocytosis (Neuroacanthocytosis)   l Chorein (VPS13A) ; Chromosome 9q21; Recessive Genetics: Mutations Japanese: Frameshift deletion Other: Missense & Nonsense Protein function: ? Protein sorting Epidemiology: Especially common in Japan Onset: 3rd to 5th decade; Mean 32 years; Range 8 to 62 years CNS Movement disorders Oro-facial-lingual dyskinesia Chorea Limbs, especially legs Frequent but not all patients Parkinsonism Cortical: Dementia; Personality disorders; Seizures (50%) Pathology Neuronal loss & Gliosis Locations: Caudate, Putamen, Pallidum & Substantia nigra   PNS Clinical Motor Distal wasting Anterior horn cell loss Sensory: Small SNAPs; Normal motor potentials Tendon reflexes: Reduced or Absent Laboratory EMG: Distal denervation Nerve pathology Distal axonopathy Loss of large myelinated axons Muscle imaging: Distal symmetric wasting Serum CK: May be elevated Acanthocytosis Differential diagnosis: A-β-lipoproteinemia; McLeod syndrome Carriers: Mild acanthocytosis

From: Leo Wang

Superficial Siderosis1 General Definition: Hemosiderin deposition along superficial (subpial) surfaces of CNS Pathogenesis Chronic bleeding into subarachnoid space Uptake of iron by astrocytes & microglia Most prominent involvement of nerves in regions with CNS myelin Underlying causes: Intracranial bleeding AVM Neoplasms: Ependymoma Dural disorders 2° surgery or trauma Neonatal intracranial hemorrhage Familial2 Cerebral cavernous angiomas Amyloidosis: Transthyretin No bleeding source: 50% Clinical features Onset: 4 months to 30 years after initial intracranial bleeding Sensorineural hearing loss (95%) Bilateral Sensorineural: Especially high tones Auditory nerve has long region of CNS myelin Cerebellar ataxia (88%) Onset usually after hearing loss Spinal cord Pyramidal signs (76%) Spinal myoclonus Sphincters: Bladder disturbance; Anal sphincter paresis Other Dementia (24%) Polyradiculopathy Anatomy: Motor; Axonal Weakness: Legs > Arms Anosmia Eye Nystagmus Ocular motility deficits: Smooth pursuit reduced Reduced Pupil reflexes (Preganglionic) Course: Slowly progressive Laboratory CSF Cells: Increased Ferritin: High Protein: High Xanthochromia MRI (T2-weighted and gradient-echo): Marked hypointensity of CNS surfaces

From M Al-Lozi Dark ring of hemosiderin deposition around cervical spinal cord (MRI-T2)