Uncommon neurological conditions and possible advances in their management

By Andrey Pashvykin

Diseases that will be discussed

• Rabies• Huntington disease• AML• Spongiform encephalopathies

Introduction

• The diseases that will be presented are not as common as other conditions but some of them are nevertheless well known

• Many of them are incurable where treatment possibilities lie only in supportive management

• The point of this discussion is to briefly describe these diseases and their experimental cures.

Huntington disease

• Autosomal dominant disease (50 percent chance of inheritance if affected parent) mutation in huntingtin gene on chromosome 4. Involves excessively repeated trinucleotide repeats causing abnormal protein formation

• Causes progressive neurological and psychiatric decline with characteristic chorea due to damage of neostriatum and other cerebral areas

• Problems include congnitive, psychomotor decline ending with dementia.

• Suicide is common and pneumonias due to muscle incoordination• Age of onset is around 40 years• Survival is about 20 years• 5-10/100,000

Treatment options

• Prenatal testing to selectively abort affected fetus. (although there are some opponents of this practice)

• Physical therapy for muscle coordination, antidepressants for depression, neuroleptics and benzodiazepenes for chorea. Antiparkinsonian drugs for hypokinesia are also used

• Tetrabenazine also recently introduced for chorea.• Novel research includes gene silencing of mutant

protein product• Also stem cell transplant into defected brain areas

AML(Lou Gehrig disease)

• Upper and lower Motor neuron disease causing muscle atrophy, fasciculations, spasticity with dysarthria and dysphagia and dyspnea. Also may cause labile effect and frontotemporal dementia

• Cause largely unknown could be linked with superoxide dismutase defect.

• Onset is around 40 years• Death at around 40 months after diagonosis(exceptions- Stephen Hawking)• 1/100000 per year

Treatment

• Supportive – includes baclofen for spasticity, physiotherapy, feeding and breathing support

• Modest effect of glutamate antagonist Riluzole in prolonging survival

• Possible advances include stem cell therapy as some trials for example in Israel took place

Transmissible Spongiform Encephalopathy

• Includes Kuru, Chronic wasting syndrome, Fatal familial insomnia , Creutzfeld Jacob disease and some others

• The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak.[16]

• Abnormal membrane protein (prion) produced PrpSc from normal PrpP causing dectruction of neurons with characteristic spongy brain pathology

• 1 case per million per year• Some are genetic in origin. Iatrogenic transmission possible as well as from food

(Mad cow disease)

• Death within 1 year usually

• Treatment involves supportive care , no cure possible• Research includes RNA interference to prevent the production of

the rogue protein and use of doxyrubicin and aphotericin B to slow the progression of disease

• Note :Recently pentosan polysulfate has gained attention as possibly being effective in the treatment of Creutzfeldt-Jakob disease (CJD), although there is currently no definitive evidence for this idea other than results of the ongoing treatment (published) of one patient in Northern Ireland and around six other patients in mainland Britain.[1]

• Around 15 other patients in non-UK countries have also received this treatment in an attempt to halt or slow down CJD and related disease progression.

Rabies

• 50000 deaths per year mostly in Asia • Causes encephalitis with hydrophobia, mania,

lethargy and death after initial flu like illness.• Transmitted by animals especially foxes, dogs, bats• The virus travels up to CNS by nerves from the site of

original bite. Once in CNS the disease is fatal with death occuring within 10 days.

• Effective vaccine is available and post exposure prophylaxis with anti-rabies immunoglobulin is available.

NEGRI BODIES -RABIES

• Historically rabies had almost universal mortality once the disease entered CNS

• But some recent advancements in management may reverse this

• The Milwakee protocol with chemically induced coma using midazolam and ketamine and administration of antivaral ribavirine is said to have saved a patient in which the CNS disease was already in progress

• This was not the only case of success and a few more patients were also cured by chemical coma protocols

Sources

• Wikipedia• http://www.algemeiner.com/2012/07/05/

orthodox-rabbi-may-be-first-als-patient-cured-by-israeli-drug/