Neurolocommotor Disorders

• Ataxia Telangiectasis (AT)

• Di sorder of neurons( HIV )
• Type 1 diabetes
• Myastheni a gr avi s (MG )
• Multiple sclerosis(MS)
Ataxia Telangiectasis
Ne urode generativ e
chil dhood d is or der
associa te d with
•Lack of coor din ation
(c erebell a ataxia ) a nd
dil atio n o f f acia l blood
vessels (t elangie ctasis) a nd
slur red s peech.
•Patie nts h ave defectiv e
mechanis ms o f D NA repair
predis posed to le ukaemias
and lymphomas
 AT cont
• Extre mely sensit ive to r adia tio n
exposure a nd s usceptible t o
chro nic respiratory in fe ctions.
• Chro nic s inopulmo nary
in fe ctio ns majo r and rela ted to
neurological a bnorm ali tie s.
• Dia gnosis c onfirm ed with
ele vated α-fe toprotein le vels
• Patients ma y b enefi t fro m
gamm a g lo buli n in fu sio ns
 Di sor der of
neurons( HI V)
Major neurological illnesses
• Toxoplasma encephalitis of the
brain (Toxoplasma gondii)
• Progressive multifocal
leukoencephalopathy (PML), a
demyelinating disease
• Cryptococcal meningitis (fungus
Cryptococcus neoformans)
• AIDS dementia complex (ADC).
 HIV neurotropism
HIV strongly neurotropic leading
to neurosychiatric disorders in
AIDS patients
HIV infected cells
• Monocyte-macrophage lineage
cells (brain)
• CTL in CSF of patients infected
• Glial cells.
Damage to neurons
Mediated by
• Macrophage liberated
monokines and enzymes
• CTL; inappropriate production of
IL-1, IL-6, TNF-α
• Platelet derived factor (PAF) by
HIV-infected macrophages.
• Virus-derived secretory factors
involved in the injury of nerve
cells.
HIV related toxic factors
HIV-related neuronal injury toxic
factors eg
• Nitric oxide (NO)
• Reactive oxygen intermediates
(ROI)
• Reactive nitrogen intermediates
(RNI)
• Arachidonic acid metabolites
(leukotreines & prostaglandins).
Type 1 diabetes
• Long term complications of IDDM
include loss of beta (β) cell function
with development of hyperglycemia;
chronic renal failure; retinal damage
leading to blindness; a leg wound
with risk of amputations;
• Accelerated c ardio vascula r
dis eases a nd n erve dama ge
le adin g t o ere ctil e dysfu nctio n.
 Mya sthenia gravis
(MG
Most common impairment of
neuromuscular transmission.
• Patients complain of muscle
weakness (eyes, face and neck,
oropharyngeal muscle weakness,
difficulty in chewing, swallowing or
talking)
• Characterized by T cell dependent
autoantibodies against nicotinic
acetylcholine receptor autoantigen (a
250 kDa glycoprotein) on the muscle
end plate.
Neuromuscular impairment
Autoantibodies
• Accelerate degradation of cross-
linked acetylcholine receptors
• Block receptor sites and inhibit
acetylcholine binding.
• ADCC and MAC mediate degradation
of cross-linked acetylcholine
receptors.
MG management
MG treated and managed using
• Standard medical therapies eg
corticosteroids, cholinesterase
inhibitors, IFN-β
• Immunosuppressive drugs
(azathioprine, cyclosporine, cyclo-
phosphamide)
• Thymectomy recommended for most
patients with MG
Multiple sclerosis
Disorder characterized by
• Progressive deterioration of the
myelin, or fatty sheaths (protect
nerve axons in CNS)
• Deterioration impairs the
transmission of nerve impulses,
resulting in weakness, numbness,
locomotors difficulty, pain and loss
of vision
MS features cont
Characterized by
• CNS perivascular inflammation, foci
of demyelination
• Elevated intrathecal production of
oligoclonal IgGs.
• T and B cells, macrophages, and
microglia implicated in contributing
to the initiation and perpetuation of
disorder
Interactions in CNS
Interaction of cells with the blood
brain barrier (BBB) under pathologic
inflammatory conditions
• Traffic of cells into the CNS in
inflammation
• Role of antigen presentation within
the CNS in the initiation, and
perpetuation of the CNS immune
response.
Multiple sclerosis
• Red blood cells in individuals
with multiple sclerosis more
vulnerable to oxidative stress
• Reduced activity of both
superoxide dismutase and
glutathione peroxidase occurs
MS and allergy
• Perivascular mast derived histamine,
protease and leukotrienes implicated
in inducing brain inflammation in MS
• Increased permeability of the blood-
brain barrier allows penetration of
immune complexes normally
prevented from direct contact with
the CNS