Neuromuscular

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Central Nervous System involvement & Neuromuscular

Antibodies
Spinal Cord
Optic nerve
Hearing loss
Cerebellum
Supratentorial
Leukodystrophy

Spinal Cord Optic Nerve & Eye Hearing loss Cerebellum Supratentorial Childhood


Leukodystrophies & Leukoencephalopathies

Multi-Infarct Dementia (CADASIL1)

  NOTCH 3 ; Chromosome 19p13.12; Dominant
Cerebral
Autosomal
Dominant
Arteriopathy with
Subcortical
Infarcts and
Leukoencephalopathy
  • Genetics
    • Allelic disorders
      • Myofibromatosis, infantile 2
      • Lateral meningocele syndrome
  • NOTCH3 protein
    • Exprression: Vessel smooth muscle
    • Binds ligands
    • Intracellular domain: Translocates to nucleus
    • Activates transcription factors
  • Clinical
    • Onset: Adult
    • Ischemic events: Recurrent; Subcortical
    • Migraine
    • Cognitive dysfunction
      • Dementia
      • Psychiatric disorders
    • Neuropathy 3
      • Clinical features: Occasional
        • Sensory loss (40%)
          • Distal
          • Symmetric
        • Weakness (30%): Distal
        • Areflexia
        • Often subclinical
      • Electrodiagnostic: Axon loss
        • NCV: Motor & Sensory
          • Mildly slow
        • CMAP & SNAP: Amplitudes low
  • Laboratory
    • MRI
      • Leukoencephalopathy
        • Especially anterior temporal
      • Subcortical infarcts
    • Pathology
      • Angiopathy (Small arterial vessels)
        • Vessel wall smooth muscle layer
          • Granular deposits
            • Congophilic
            • PAS+
        • Locations
          • Brain; Skin; Muscle; Nerve
      • Peripheral nerve

From: R Schmidt MD
CADASIL
Vessel in Brain

From: R Schmidt MD
CADASIL
Skin Vessels


From: R Schmidt MD
CADASIL
Granules in Skin Vessels
  May contain NOTCH3

From: R Schmidt MD

Chorea-Acanthocytosis (Neuroacanthocytosis; CHAC)

  Vacuolar protein sorting 13, yeast, homolog of, A (VPS13A;Chorein) ; Chromosome 9q21.2; Recessive
  • Epidemiology: Especially common in Japan
  • Genetics: Mutations
    • Japanese: Frameshift 260-BP deletion
    • Other: Missense & Nonsense
  • VPS13A Protein
  • Clinical
    • 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
      • Motor
        • Distal wasting
        • Anterior horn cell loss
      • Tendon reflexes: Reduced or Absent
  • Laboratory
    • EMG: Distal denervation
    • NCV
      • Sensory: Small SNAPs
      • Motor potentials: Normal
    • Nerve pathology
      • Distal axonopathy
      • Loss of large myelinated axons
    • Muscle imaging: Distal symmetric wasting
    • Serum CK: May be elevated
    • Brain MRI
      • Head of caudate nuclei & putamen: Atrophy
        • Hyperintense in T2
        • Isointense in T1
      • SWI positive iron deposition: Some patients
      • Adults
        • White matter: T2 signal; Cerebral peduncles & Corpus callosum
        • Other: Basal ganglia, Thalamus, Pons
    • Blood: Acanthocytosis

From: Leo Wang

Intellectual Developmental Disorder ± Peripheral neuropathy (IDDPN)

  Nudix Hydrolase 2 (NUDT2; APAH1) ; Chromosome 9p13.3; Recessive

Superficial Siderosis 1

  • 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
      • Familial 2
        • 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)

Return to Polyneuropathy Index

References
1. J Neurol 2001;248:63-64 ; J Neurol 2001;248:1099-1100, Neurology 1999;53:1130
2. Am J Med Genet 2004;130A:22-25
3. J Neurol 2005; Online April

4/28/2022