Anterior Horn Cell Disorders Shekhar J.Lamdhade Shekhar J.Lamdhade Consultant Neurologist Consultant Neurologist Al Amiri Hospital Al Amiri Hospital

Anterior Horn Cell Disorders * Classification * Amyotrophic Lateral Sclerosis (ALS) - clinical manifestations, - differential diagnosis, - treatment

Anterior horn ≈ Motor Neuron Disorders ≈ Degeneration (MND) MND – Progressive degeneration of neurons of motor cortex, brain stem, and spinal cord Manifested by Weakness, atrophy (LMN) and corticospinal tract signs (UMN)

Amyotrophic lateral sclerosis (ALS) is uncommon. It begins in middle age and proceeds to death in several years. There is loss of anterior horn cells, so that patients present with progressive weakness that proceeds to paralysis from neurogenic muscular atrophy. Because of the loss of anterior horn cells, the anterior (ventral) spinal motor nerve roots demonstrate atrophy, as seen here in comparison with a normal spinal cord.

Types: SMA (Spinal muscular atrophy) (Congenital form) SMA - I - Infantile SMA - I - Infantile SMA- II - Childhood SMA- II - Childhood SMA III - Adolescence SMA III - Adolescence C/F: floppy baby, generalized poor muscular development, sluggish reflexes. Delayed motor mile stones, feeding & respiratory difficulties, recurrent aspirations death. Defect: Mutation in SMN gene

Motor Neuron secretes Trophic factor

Motor Neuron Disease Types 1. Amyotrophic Lateral Sclerosis ( ALS) 2. Progressive spinal muscular atrophy 3. Progressive bulbar palsy 4. Primary lateral sclerosis

1. Amyotrophic Lateral Sclerosis (ALS) Most frequent form: Muscular atrophy and hyper reflexia. 2. Progressive spinal muscular atrophy: Diffuse muscular weakness and atrophy - specially of spinal muscles. Diffuse muscular weakness and atrophy - specially of spinal muscles.

3. Progressive bulbar palsy: Weakness & wasting in muscles innervated by motor nuclei of lower brain stem – jaw, face, tongue, pharynx and larynx. 4. Primary lateral sclerosis: Predominant spastic weakness, hyperreflexia, Babinski sign. LMN signs none or very late.

ALS ( Amyotrophic Lateral Sclerosis) Charcot – 1869 Incidence : /100,000 M=F World wide Some clustering of cases in Kii peninsula of Japan & Guam. 10% familial cases, AD type

ALS – Clinical features Weakness begins in one limb, distally. Unexplained tripping – mild foot drop Difficulty in using fingers – using key. Unexplained cramps & fasciculations: shoulder – arm- fore arm, thighs-leg-foot thighs-leg-foot

ALS – Clinical features Wasting of small muscles of hands : Abductors, adductors, extensors more weak than flexors. - CLAW HAND. - CLAW HAND. DTR: hyper/ hypo, Babinski sign + ve, Preserved abdominal reflexes Late – involvment of neck, pharynx and larynx. Course : Progressive, 90% die in 6 years

The hallmark of motor neuron disease is denervation and atrophy of muscle due to loss of spinal motor neurons (Courtesy of Samar Hasnain)

PBP (Progressive bulbar palsy) 25% patients starts as PBP. Dysarthria, absent gag reflex. Dysphagia – unable to swallow food/liquids. Atrophy of tongue, Jaw jerk brisk or absent. Pseudo bulbar signs – pathological laughter or cry. Weak Respiratory Muscles: breathing difficulty, aspiration pneumonias, Respiratory failure in 2-3 years

Tongue in ALS:Weak with little wasting At rest & Attempted protrusion

PMA (Progressive muscular atrophy) M:F – 4:1 Slower course, better prognosis in young onset patients. Symmetrical weakness, absent or sluggish reflexes D/D: Motor neuropathy – immune mediated, paraproteinemia, IgM antibodies against GM ganglioside. Focal conduction blocks, sensory abnormalities on EMG/ NCS

PLS (Progressive lateral sclerosis) Rare. Pure spastic involvement. 5-6 decade LL UL bulbar involvement * No ocular muscle involvement. * No bladder impairment.

D/D * Multiple sclerosis (MS) – optic nerve, cerebellum, bladder, sensory features. Diagnostic - CSF and MRI. *Slow compression of spinal cord – meningioma, syryngomyelia – MRI.

D/D *Lyme disease – rare, serum antibodies. *HIV myelopathy – history/other features / serum Antibodies / MRI. *B12 deficiency – sensory involvement/ Nerve conduction abnormalities, low serum b12. * Inclusion body myositis – muscle biopsy

D/D Bulbar weakness : *Myasthenia gravis - fatigability, serum Ach receptor antibodies, positive Tensilon test, decremental pattern on EMG/NCS *Polio myelitis - Acute viral illness, juvenile onset, epidemic, abnormal CSF, positive serum antibodies. *Muscular dystrophy - High CK, muscle biopsy

Pathogenesis: Largely unknown SOD 1 mutation (superoxide dysmutase) Excitotoxic glutaminergic activity and mitochondrial dysfunction

Treatment : Mainly Supportive RILUZOLE : Anti glutaminergic : used in bulbar onset patients : used in bulbar onset patients : prolongs disease by 3- 4 months : prolongs disease by 3- 4 months The only specific drug.

Treatment : Spasticity : Baclofen, Tizanidine, Valium Spasticity : Baclofen, Tizanidine, Valium Physiotherapy, breathing exercises. Respiratory support : BIPAP, tracheostomy, ventilatory support Feeding : Nasogastric (NG) tube, PEG ( Percutaneous endoscopic gastrostomy) PEG ( Percutaneous endoscopic gastrostomy)

Renowned scientist Stephen Hawking suffers from amyotrophic lateral sclerosis. (Reproduced by permission of AP/Wide World Photos))

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