Motor Neuron Disease

Kefah Al-Hayek, MD J.U.S.T.

Definitions

Motor neuron diseases:

Progressive degeneration and loss of motor neurons in the spinal cord with or without similar lesions in the motor nuclei of the brainstem or the motor cortex

Motor neuron disease = Amyotrophic lateral sclerosis Spinal muscular atrophy:

Only lower motor neuron signs

Amyotrophic lateral sclerosis (ALS)

A= without Myo= Muscle Trophic= Nourishment Lateral= side of the spinal cord Sclerosis= Hardening or scaring

ALS

Also known as Lou Gehrigs disease Degeneration of UMN and LMN Accuracy of clinical diagnosis ~ 95%

Epidemiology

Worldwide roughly the same prevalence 50 X lO-6 No identified consistent risk factors related to occupation, trauma, diet, or socioeconomic status Generally begins in 30-60s 5% of cases are familial in an autosomal dominant pattern

20% of familial cases map to ch. 21; mutations in the gene for superoxide dismutase (SOD)

Dementia and parkinsonism seem to increase in firstdegree relatives of patients with ALS

Pathogenesis

Sporadic ALS unknown Environmental factors have been suspected (Guam) Glutamate toxicity

Clinical Manifestations

Weakness : legs, hands, proximal arms, oropharynx Fasciculation Often hands are affected first, usually asymmetrically

Clinical Manifestations

Clinical Manifestations

Footdrop Muscle cramps (hypersensitivity of denervated muscle) Weight loss Respiration is usually affected late

Clinical Manifestations

Clinical Manifestations

Sensation is not clinically affected Bladder function is spared Combination of overactive reflexes with Hoffmann signs in arms with weak, wasted, and fasciculating muscles is virtually pathognomonic of ALS

Clinical Manifestations

Course is relentless and progressive without remissions, relapses, or even stable plateaus Death from respiratory failure, aspiration pneumonitis, or pulmonary embolism Mean duration of symptoms is about 4 years (27-43 months) ; 20% live > 5 years

Clinical Classification: I- Sporadic

Primary Lateral Sclerosis

Purely UMN Bilateral involvement of corticobulbar pathways Pseudobulbar affect Prominent dysarthria and dysphagia (LMN) LMN in limbs; anterior horn cell degeneration

Pseudobulbar Palsy

Progressive bulbar palsy

Progressive Spinal Muscular atrophy

Clinical Classification

II- Familial

AD AR X-linked

III- ALS-Parkinsonism-dementia complex

Laboratory Data

EMG evidence of active denervation in at least three limbs Nerve conduction velocities should be normal or nearly so Conduction block is rare in patients with frank upper motor neuron signs

Laboratory Data

MRI brain and spine CBC, KFT, LFT, TFT, serum electrophoresis Anti-GM1 antibodies

Diagnosis

Body divided into regions: Bulbar, cervical, thoracic and lumbosacral UMN & LMN signs in three regions

DDx

Multifocal motor neuropathy with conduction block

Conduction block in more than one nerve and not at sites of entrapment neuropathy Primarily affects the hands Asymmetric Men much more often than women Predominantly lower motor neuron Progresses more slowly than ALS Immunosuppressive drug therapy IVIG

DDx

Myasthenia gravis (MG)

Dysarthria and dysphagia Same age group as ALS Ptosis, ophthalmoparesis, diurnal fluctuation and remissions

DDx

Cervical spondylosis

Neck pain Sensory symptoms or signs in the hands No fasciculations in legs or tongue

DDx

MS B12 def HIV Pseudobulbar Palsy (MS and bilateral strokes) Benign fasciculation and cramps

Medical students, physicians, and other medical workers No weakness nor wasting ALS almost never start with this syndrome

Rx

No effective drug therapy Riluzole (Rilutek)

Glutamate inhibitor Prolongs life by 3 to 6 months No visible effect on function or quality of life

Symptomatic (sialorrhea, dysphagia, tracheostomy) Emotional support Immunosuppressive therapy

Only for lymphoproliferatlve disease, monoclonal gammopathy, conduction block or high titers of antibodies to GM, or MAG

Famous people with ALS

Steven Hawking: Smartest man alive Proved Einstein's Theory of Relativity He currently uses an electric wheelchair to get around A computerized voice synthesizer operated by facial muscles in order to speak