El Paso, TX. Chiropractor, Dr. Alexander Jimenez focuses on degenerative and demyelinating diseases of the nervous system, their symptoms, causes and treatment.

Degenerative & Demyelinating Diseases

Motor Neuron Diseases

• Motor weakness without sensory changes
• Amyotrophic lateral sclerosis (ALS)
• ALS Variants
• Primary lateral sclerosis
• Progressive bulbar palsy
• Inherited conditions that cause anterior horn cell degeneration
• Werdnig-Hoffmann disease in infants
• Kugelberg-Welander disease in children and young adults

Amyotrophic Lateral Sclerosis (ALS)

• Affects patients 40-60 years of age
• Damage to:
• Anterior horn cells
• Cranial nerve motor nuclei
• Corticobulbar and corticospinal tracts
• Lower motor neuron findings (atrophy, fasciculations) AND upper motor neuron findings (spasticity, hyperreflexia)
• Survival ~three years
• Death results from weakness of the bulbar and respiratory musculature and resultant superimposed infection

ALS Variants

• Usually eventually evolve into typical ALS pattern
• Primary Lateral Sclerosis
• Upper motor neuron signs begin first, but patients do eventually have lower motor neuron signs as well
• Survival can be ten years or longer
• Progressive Bulbar Palsy
• Selectively involves the head and neck musculature

Inherited Motor Neuron Conditions

• Anterior horn cell degeneration
• Werdnig-Hoffmann disease
• Affects infants
• Kugelberg-Welander disease
• Affects children and young adults

Church, Archibald. Nervous and Mental Diseases. W.B. Saunders Co., 1923.

Alzheimer Disease

• Characterized by neurofibrillary tangles (aggregates of hyperphosphorylated tau protein) & beta-amyloid plaques
• Generally occurring after age 65
• Hereditary risk factors
• Mutations in the beta amyloid gene
• Epsilon 4 version of apolipoprotein

Diagnosis

• Pathologic diagnosis is the only way to definitively diagnose the condition
• Imaging may be able to rule out other causes of dementia
• Functional imaging studies may be further developed to become diagnostically useful in the future
• CSF studies examining for tau proteins and beta amyloid may become useful as diagnostic tests in the future

Amyloid Plaques & Neurofibrillary Tangles

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Brain Areas Affected by Alzheimer Disease

• Hippocampus

• Loss of recent memory

• Posterior temporo-parietal association area

• Mild anomia & constructional apraxia

• Nucleus basalis of Meynert (cholinergic neurons)

• Changes in visual perception

Progression

• As more and more cortical areas become involved, the patient will develop more severe cognitive deficits, however paresis, sensory loss, or visual field defects are features.

Treatment Options

• Medications that inhibit central nervous system acetylcholinesterase

• Donepezil
• Galantamine
• Rivastigmine

• Aerobic Exercise, 30 minutes daily

• PT/OT care to maintain activities of daily living

• Antioxidant and anti-inflammatory therapies
• In advanced stages, may require full time, in home care

Vascular Dementia

• Cerebral arteriosclerosis leading to stroke
• Patient will have documented stroke history or signs of prior stroke (spasticity, paresis, pseudobulbar palsies, aphasia)
• May be associated with Alzheimer Disease if due to amyloid angiopathy

Frontotemporal Dementia (Pick’s Disease)

• Familial

• Affects the frontal and temporal lobes

• May be seen on imaging if advanced degeneration in these areas

• Symptoms

• Apathy

• Disordered behavior

• Agitation
• Socially inappropriate behavior
• Impulsivity

• Language difficulties

• Generally no memory or spatial difficulties

• Pathology reveals Pick bodies within the neurons

• Results in death in 2-10 years

Pick Bodies/Cytoplasmic Inclusions

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Treatment

• Antidepressants

• Sertraline
• Citalopram

• Discontinue medications that can cause memory impairment or confusion

• Sedatives
• Benzodiazepines

• Exercise

• Lifestyle modification
• Behavioral modification therapy

Parkinson Disease

• May occur at any age, but rare before age 30, and increases prevalence increases in older populations

• Familial tendency but can also without family history

• Can be induced by certain environmental factors

• Exposure 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
• Compounds which produce excessive free radicals

• Affects substantia nigra pars compacta

• Dopaminergic neurons

• On pathology, the presence of Lewy Bodies

• Accumulation of alpha-synuclein

Lewy Bodies

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Symptoms of Parkinsonism

• Rigidity (all planes)

• Passive ROM
• Active movement
• May be of cogwheel nature due to tremor symptoms

• Bradykinesia

• Slowness of movement
• Inability to initiate movement
• Freezing

• Resting tremor (“pill-rolling”)

• Created by oscillation of opposing muscle groups

• Postural defects

• Anteriorly flexed (stooped) posture
• Inability to compensate for perturbations, resulting in retropulsion

• Mask-like facies

• Mild to moderate dementia

• Later in progression, due to lewy body accumulation

Pathology

• Deficiency of dopamine in the striatum (caudate and putamen) of the basal ganglia

• Dopamine normally has the effect of stimulating the direct circuit through the basal ganglia, while inhibiting the indirect pathway

Carbidopa/Levodopa

• Most common treatment is a combination drug

• Levodopa

• A dopamine precursor that crosses the blood-brain barrier

• Carbidopa

• Dopamine decarboxylase inhibitor that does not cross the BBB
• Amino acids will reduce effectiveness (competition) and so medication should be taken away from protein

Prolonged Treatment With Carbidopa/Levodopa

• The patient’s capacity to store dopamine declines with medication use and therefore the improvements from the medications will last for shorter and shorter periods the longer the medication is used

• Over time can result in proliferation of dopamine receptors

• Peak-dose dyskinesia

• Long term use puts stress on the liver

• Other side effects can include nausea, hypotension and hallucinations

Other Treatment Options

• Medications

• Anticholinergics
• Dopamine agonists
• Dopanime breakdown inhibitors (Monoamine oxidase or catechol-O-methyl transferase inhibitors)
• High dose glutathione

• Brain balancing functional neuro-rehab exercises

• Vibration
• Retropulsive stimulation
• Repeated reflex stimulation
• Targeted CMT/OMT

Multiple System Atrophy

• Symptoms of Parkinson Disease paired with one or more of the following:

• Pyramidal signs (Striatonigral degeneration)
• Autonomic dysfunction (ShyDrager syndrome)
• Cerebellar finding (Olivopontocerebellar atrophy)

• Generally not responsive to standard Parkinson Disease treatments

Progressive Supranuclear Palsy

• Fast progressing degeneration involving tau proteins in many areas including the rostral midbrain

• Symptoms usually start around ages 50-60

• Gait difficulty

• Significant dysarthria

• Voluntary vertical gaze difficulty

• Retrocollis (dystonic extension of the neck)

• Severe dysphagia

• Emotional lability

• Personality changes

• Cognitive difficulty

• Does not respond well to standard PD treatment

Diffuse Lewy Body Disease

• Progressive dementia
• Severe hallucinations and possible paranoid delusions
• Confusion
• Parkinsonian symptoms

Multiple Sclerosis

• Multiple white matter lesions (plaques of demyelination) in the CNS

• Variable in size
• Well-circumscribed
• Visible on MRI

• Optic nerve lesions are common

• Peripheral nerves are not involved

• Uncommon in children under 10, but usually presents before age 55

• Viral infection may trigger an inappropriate immune response with antibodies to a common virus-myelin antigen

• Infectious and immune mechanisms contribute

Types Of MS

• Primary progressive MS (PPMS)

• Secondary progressive MS (SPMS)

• Relapsingremitting multiple sclerasis (RRMS)

• Most common type
• Can develop acutely, spontaneous appear to resolve and return
• Eventually becomes like SPMS

Optic Nerve Involvement

• In 40% of MS cases

• Pain with eye movements

• Visual field defect (central or paracentral scotoma)

• Funduscopic examination

• May reveal papilledema if the plaque involves the optic disk
• May not appear unusual if plaques are behind the optic disk (retrobulbar neuritis)

Medial Longitudinal Fasciculus Involvement

• Demyelination of the MLF results in internuclear ophthalmoplegia

• During lateral gaze there is paresis of the medial rectus and nystagmus of the contralateral eye

• Convergence remains normal

Other Possible MS Symptoms

• Myelopathy

• Spastic hemiparesis
• Impaired sensory tracts (DC-ML)
• Paresthesias

• Cerebellar involvement

• Ataxia
• Dysarthria

• Vestibular system involvement

• Imbalance
• Mild vertigo
• Nystagmus

• Tic douloureux (trigeminal neuralgia)

• Lhermitte’s symptom

• Shooting or tingling sensation referred to the trunk and limbs during neck flexion
• Fatigue
• Hot bath often exacerbates symptoms

Differentials To Consider

• Multiple emboli and vasculitis

• May appear as white matter damage on MRI

• Central nervous system sarcoidosis

• Can produce reversible optic neuritis and other CNS signs

• Whipple disease

• Inflammatory lesions
• Usual eye movements

• Vitamin B12 deficiency

• Dementia
• Spasticity
• Dorsal column

• Meningovascular syphilis

• Multifocal CNS damage

• CNS Lyme disease

• Multifocal disease

Differential Diagnosis: Diagnostic Studies

• Blood tests can help to distinguish

• Complete blood count
• Antinuclear antibodies (ANA)
• Serum test for syphilis (RPR, VDRL, etc.)
• Fluorescent treponemal antibody test
• Lyme titer
• ESR
• Angiotensin converting enzyme level (to r/o sarcoidosis)

Diagnostic Studies Of MS

• MRI with and without contrast

• 90% of MS cases have detectable MRI findings

• CSF findings

• Elevation of mononuclear white blood cells
• Oligoclonal IgG bands

• Increased globulin to albumin ratio

• This is also seen in 90% of MS cases

• Increased myelin basic protein levels

Prognosis

• Average survival after diagnosis is ~ 15 to 20 year
• Death is usually from superimposed infection and not due to the effects of the disease itself

Sources

Alexander G. Reeves, A. & Swenson, R. Disorders of the Nervous System. Dartmouth, 2004.
Swenson, R. Degenerative Diseases of the Nervous System. 2010.