mnd - other than als

8/6/2019 MND - other than ALS

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OTHER MOTOR NEURONOTHER MOTOR NEURON

DISEASESDISEASES

LOWER MOTOR NEURON DISORDERS

The peripheral motor neurons are affectedwithout evidence of involvement of the corticospinal

motor system



XX--LinkedLinked SpinobulbarSpinobulbar MuscularMuscular

Atrophy (Kennedy's Disease)Atrophy (Kennedy's Disease)

y Progressive weakness and wasting of

limb and bulbar muscles begins in males inmid-adult life and is conjoined with

androgen insensitivity manifested by

gynecomastia and reduced fertility



y Distinguishing features from ALS-absence

of spasticity and presence of subtle

sensory neuropathy.

y The underlying molecular defect is an

expanded trinucleotide repeat (-CAG-) in

the first exon of the androgen receptorgene on the X chromosome.



AdultAdult TayTay--Sach'sSach's DiseaseDisease

y Arising from deficiency of the enzyme B-

hexosaminidase (hex A).

y They are very slowly progressive .

y Dysarthria and radiographically evident

cerebellar atrophy may be prominent.



Spinal Muscular AtrophySpinal Muscular Atrophy

y Early onset

y Defect in the majority of families with

SMA maps to a locus on chromosome 5

encoding a putative motor neuron

survival protein (SMN, for survival motor

neuron)

y Characterized by extensive loss of largemotor neurons; muscle biopsy reveals

evidence of denervation atrophy.



Multifocal Motor Neuropathy withMultifocal Motor Neuropathy with

Conduction Block Conduction Block

y Lower motor neuron function isregionally and chronically disrupted byremarkably focal blocks in conduction.

y Elevated serum titers of mono- andpolyclonal antibodies to ganglioside GM1;which produce selective, focal, paranodal

demyelination of motor neurons.y Respond dramatically IV immunoglobulin

or chemotherapy



SELECTED DISORDERS OF THESELECTED DISORDERS OF THE

UPPER MOTOR NEURONUPPER MOTOR NEURON

y Primary Lateral Sclerosis



y Rare disorder arising sporadically in adults

in mid- to late life.

y Characterized by progressive spastic

weakness of the limbs, preceded or

followed by spastic dysarthria and

dysphagia, indicating combined

involvement of the corticospinal andcorticobulbar tracts.

Primary Lateral SclerosisPrimary Lateral Sclerosis



y Neuropathologic examination reveals loss

of the large pyramidal cells in the

precentral gyrus and degeneration of the

corticospinal and corticobulbarprojections.

y Variable course.



FAMILIAL SPASTIC PARAPLEGIAFAMILIAL SPASTIC PARAPLEGIA

y Autosomal trait usually.

ySymptoms -progressive spastic

weakness beginning in the distal lowerextremities.

y Respiratory function is spared-Has a long

survival.

y Late in the illness there may be urinary

urgency and incontinence and sometimes

fecal incontinence



yWhen recessively inherited- altered

corticospinal and dorsal column function

accompanied by amyotrophy, mental

retardation, optic atrophy, and sensoryneuropathy.



NEUROPATHOLOGYNEUROPATHOLOGY

y Degeneration of the corticospinal tracts,

which appear nearly normal in the

brainstem but show increasing atrophy at

more caudal levels in the spinal cord-distal axonopathy of long neuronal

f ibers within the CNS.



y Eleven FSP genes have been identified.

y Spastin-The gene most commonlyimplicated in dominantly inherited FSP,

encodes a microtubule interacting protein.

y

Atlastin-The most common childhood-onset dominant form arises from mutations

in this gene.

y Gene for myelin proteolipid protein-

mutation causes X-linked recessive FSP.

y par apleg in gene- recessive variant.



THANK YOUTHANK YOU

mnd - other than als

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