Demyelination vs Dysmyelination

Demyelination is a term used to describe the destruction of a substance called myelin that surrounds axonal fibres. This is caused by diseases that damage the myelin sheath or the cells that form it.

One of most common forms of autoimmune demyelinating disease is MS.Other autoimmune disorders that can cause demyelination include transverse myelitis, acute disseminated encephalomyelitis, Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, central pontine myelinosis, Charcot Marie Tooth disease and leukodystrophy.

Dysmyelination on the other hand, is a term used to describe the defective structure and function of myelin sheaths. Unlike demyelination, nerve lesions are not a feature of dysmyelination.

Dysmyelination disorders often arise from hereditary mutations that affect the synthesis and formation of myelin. The disorders can be categorized into those that affect mainly the white brain matter and those that affect both the white and grey matter. Dysmyelination disorders are also referred to as leukodystrophies and the most common example is metachromatic leukodystrophy.

Hallervorden-Spatz Disease

Presentation

History

Symptoms in Hallervorden-Spatz disease (HSD) include the following:

• Dystonia - A prominent and early feature
• Significant speech disturbances - Can occur early
• Dysphagia - A common symptom; caused by rigidity and corticobulbar involvement
• Dementia - Present in most individuals with HSD
• Visual impairment - Caused by optic atrophy or retinal degeneration; not uncommon and can be the presenting symptom of the disease, although this is rare
• Seizures - Have been described [18]

Clinical manifestations of HSD vary from patient to patient. The symptoms usually begin in the first decade with a motor disorder of extrapyramidal type and gait difficulty. Extrapyramidal symptoms dominate the clinical picture and include rigidity, slowness of movement, dystonia, choreoathetosis, and tremor.

In some patients, extrapyramidal dysfunction may be delayed for several years, and spasticity and dysarthria may be the presenting symptoms.

Physical Examination

Physical examination reveals signs consistent with extrapyramidal and corticospinal dysfunction. In addition to rigidity, dystonia, and chorea, patients may exhibit spasticity, brisk reflexes, and extensor plantar responses.

Based on the common clinical features, the following diagnostic criteria for HSD have been proposed.[18] For a definitive diagnosis, all of the obligate findings and at least 2 of the corroborative findings should be present. None of the exclusionary factors should be present.

Obligate features of HSD include the following:

• Onset during the first 2 decades of life
• Progression of signs and symptoms
• Evidence of extrapyramidal dysfunction, including 1 or more of the following: dystonia, rigidity, choreoathetosis

Corroborative features include the following:

• Corticospinal tract involvement
• Progressive intellectual impairment
• Retinitis pigmentosa and/or optic atrophy
• Seizures
• Positive family history consistent with autosomal recessive inheritance
• Hypointense areas on magnetic resonance imaging (MRI) involving the basal ganglia
• Abnormal cytosomes in circulating lymphocytes and/or sea-blue histiocytes in bone marrow

Exclusionary features include the following:

• Abnormal ceruloplasmin levels and/or abnormalities in copper metabolism
• Presence of overt neuronal ceroid lipofuscinosis, as demonstrated by severe visual impairment and/or seizures that are difficult to control
• Predominant epileptic symptoms
• Severe retinal degeneration or visual impairment preceding other symptoms
• Presence of familial history of Huntington chorea and/or other autosomal, dominantly inherited neuromovement disorders
• Presence of caudate atrophy on imaging studies
• Deficiency of hexosaminidase A
• Deficiency of ganglioside monosialic acid-1 (GM1)–galactosidase
• Nonprogressive course
• Absence of extrapyramidal signs

Balo's Concentric Sclerosis

Balo's Concentric Sclerosis is an uncommon demyelinating disease.
It is characterized by alternative bands of demyelination and myelin preservation, often in whorl-like configurations.

Here T2 and postcontrast T1W images showing a large lesion in the left hemisphere with alternating T2-hyperintense and isointense bands.
On the T1W images after gadolinium there is alternating linear enhancement.
There is a smaller, similar lesion on the right.

LETM MRI (longitudinally extensive transverse myelitis)

Detection of a LETM spinal cord lesion associated with acute myelitis is the most specific neuroimaging characteristic of NMOSD (>3 vertebral segment longitudinally extensive transverse myelitis lesions)

(LETM) in NMO

Such lesions typically involve
—the central gray matter—cord swelling, —central hypointensity on T1- weighted sequences, and —enhancement following IV gadolinium administration; —extension of a cervical lesion into the brainstem is characteristic.

LETM pattern is characteristic of NMOSD - —7%–14% of initial and 8% of subsequent myelitis attacks in AQP4-IgG-seropositive patients do not meet the LETM definition.

LETM MRI pattern may also occur in patients with
infectious,
granulomatous,
neoplastic, and
paraneoplastic diseases,
acute disseminated encephalomyelitis (ADEM),
spinal cord infarction,
and dural arteriovenous fistula

Adson's sign

ADSON'S SIGN

 

Adson's sign is the loss of the radial pulse in the arm by rotating head to the ipsilateral side with extended neck following deep inspiration. This is accompanied by compression of the Subclavian artery by a cervical rib or tightened anterior and middle scalene muscles. Thoracic outlet obstruction may be caused by a number of abnormalities, including degenerative or bony disorders, trauma to the cervical spine, fibromuscular bands, vascular abnormalities, and spasm of the anterior scalene muscle. Symptoms are due to compression of the brachial plexus and subclavian vasculature, and consist of complaints ranging from diffuse arm pain to a sensation of arm fatigue, frequently aggravated by carrying anything in the ipsilateral hand or doing overhead work such as window cleaning.

Performed as follows

1. Patient in upright position.
2. Passively extend, abduct and externally rotate affected arm while palpating the radial pulse.
3. Ask patient to take a deep breath and hold it in.
4. Ask patient to extend neck and rotate the head towards affected side.

The test is positive if there is a marked decrease, or disappearance, of the radial pulse. It is important to check the patient's radial pulse on the other arm to recognize the patient's normal pulse. It is/was sometimes used as a sign of thoracic outlet syndrome (TOS). Adson's sign is no longer used as a positive diagnosis of TOS since many people without TOS will show a positive Adson's.

There is minimal evidence of interexaminer reliability.

It is named after Alfred Washington Adson.

Brown syndrome

1. Brown syndrome is a rare form of strabismus characterized by limited elevation of the affected eye.  It is a mechanical problem in which the superior oblique muscle/tendon (on the outside of the eyeball) is unable to lengthen and therefore does not move freely. This makes looking up and in with the affected eye difficult. Often the higher eye is mistakenly presumed to be the abnormal eye, but it is actually the lower eye that is affected. Brown syndrome causes the affected eye to have trouble looking upward and inwards towards the nose. Essentially the affected eye is “tethered” or held down by the tight superior oblique tendon.The disorder may be congenital (existing at or before birth), or acquired.Acquired Brown syndrome is uncommon but may be seen following surgery, after trauma or in association with inflammatory diseases. Trauma can cause a Brown Syndrome if a blunt object hits the eye socket in the upper inside corner near the nose. Surgery for the eyelid, frontal sinus, eyeball (retinal detachment) and teeth (dental extraction) have been linked to acquired Brown syndrome. Inflammation of the tendon-trochlea complex (from adult and juvenile rheumatoid arthritis, systemic lupus erythematosus and sinusitis) can be associated with development of the problem. Sometimes the cause is never identified.Hereditary cases of Brown syndrome are rare. Most cases arise without a family history (sporadic).
2. Harold W. Brown characterized the syndrome in many ways such as:

   • Limited elevation in the eye when head is straight up
   • Eyes point out in a straight up gaze (divergence in up gaze)
   • Widening of the eyelids in the affected eye on adduction
   • Head tilts backwards (compensatory chin elevation to avoid double vision)
   • Near normal elevation in abduction.

   
   

   Brown syndrome can be classified according to severity. In mild cases there is a reduced ability to look up and in with the affected eye. In moderate cases, there is also a tendency for the eye to move downward as it moves inward. In severe cases there is a tendency for the affected eye to turn downward when the patient looks straight ahead.
3. In Brown's original series there was a 3:2 predominance of women to men. Ninety percent of patients have only one affected eye, more commonly the right. Treatment recommendations for Brown syndrome vary according to the cause and severity of the movement disorder. Close observation alone is usually sufficient in mild cases. Visual acuity and the ability to use both eyes at the same time (binocular vision) should be monitored closely in young children. Nonsurgical treatment is often advised for recently acquired, traumatic and variable cases. Systemic and locally injected corticosteroids have been used to treat inflammatory cases of acquired Brown syndrome. Non-steroidal anti-inflammatory agents (like ibuprofen) have also been used. Surgical treatment is usually recommended if any of the following are present: eye misalignment when looking straight ahead, significant double vision, compromised binocular vision or pronounced abnormal head position. More than one surgery may be needed for optimal management.The goal of surgery is to restore free ocular rotations. Various surgical techniques have been used:
• Harold Brown advocated that the superior oblique tendon be stripped. A procedure named sheathotomy. The results of such a procedure are frequently unsatisfactory because of reformation of scar tissue.
• Tenotomy of the superior oblique tendon (with or with out a tendon spacer) has also been advocated. This has the disadvantage that it frequently produces a superior oblique paresis.
• Weakening of the inferior oblique muscle of the affected eye may be needed to compensate for iatrogenic fourth nerve palsy. 

1. It's also known as Superior Oblique Tendon Sheath syndrome. Not to be confused with Brown-Vialetto-Van Laere syndrome.

Cerebral perfusion pressure

Cerebral perfusion pressure (CPP), the pressure of blood flowing to the brain, is normally fairly constant due to autoregulation, but for abnormal mean arterial pressure (MAP) or abnormal ICP the cerebral perfusion pressure is calculated by subtracting the intracranial pressure from the mean arterial pressure: CPP = MAP − ICP 

Monro-Kellie hypothesis

Monro-Kellie doctrine, or hypothesis, is that the sum of volumes of brain, CSF, and intracranial blood is constant. An increase in one should cause a decrease in one or both of the remaining two. This hypothesis has substantial theoretical implications in increased intracranial pressure and in decreased CSF volume. Many of the MRI abnormalities seen in intracranial hypotension or CSF volume depletion can be explained by the Monro-Kellie hypothesis. These abnormalities include meningeal enhancement, subdural fluid collections, engorgement of cerebral venous sinuses, prominence of the spinal epidural venous plexus, and enlargement of the pituitary gland.

Bell Magendie Law

Bell Magendie Law

In anatomy and neurophysiology, this is the finding that the anterior spinal nerve roots contain only motor fibers and posterior roots only sensory fibers and that nerve impulses are conducted in only one direction in each case.

Exception- The unmyelinated Group C nerve fibers that transmit pain and temperature from the pelvic viscera enter the spinal cord via ventral roots at L5-S3, thus violating the Bell–Magendie law.

Mc Donald Criteria 2010

Sites of Locked in syndrome (deefferantation)

Sites of Locked in syndrome (deefferantation)

1. Basilar artery occlusion
2. B/L ventral pontine lesion
3. Polyneuritis
4. Myasthenia gravis
5. Polio
6. GB Syndrome

Sites causing Ataxic Hemiparesis

Sites causing Ataxic Hemiparesis

1. C/L thalamocapsular
2. C/L posterior limb of internal capsule
3. C/L red nucleus
4. C/L basis pontis- juntion of upper third and lower two thirds
5. Superficial ACA supplying paracentral area

Sites of Dysarthria- Clumsy Hand Syndrome

Sites of Dysarthria- Clumsy Hand Syndrome

1. Genu of internal capsule
2. Small deep cerebellar hemorrhage
3. Basis pontis at junction of upper third and lower two third

Sites of Pure Motor Hemiparesis

Sites of Pure Motor Hemiparesis

A. Intracranial-
1. Posterior limb of Internal Capsule
2. Cerebral Peduncle
3. Medullary pyramid.
4. Basis pontis 

House-Brackmann scale

The House-Brackmann scale is a facial nerve grading system, at one end of the scale there is normal facial nerve function and at the other there is complete paralysis.

Grade	FunctionLevel	Symmetry at Rest	Eye(s)	Mouth	Forehead
I	Normal	Normal	Normal	Normal	Normal
II	Mild	Normal	Easy and complete closure	Slightly asymmetrical	Reasonable function
III	Moderate	Normal	With effort, complete closure	Slightly affected with effort	Slight to Moderate movement
IV	Moderately Severe	Normal	Incomplete closure	Asymmetrical with maximum effort	None
V	Severe	Asymmetry	Incomplete closure	Minimal Movement	None
VI	Total Paralysis	Total Paralysis

Complications of IvIg infusion

Nephrotic syndrome
Aseptic meningitis
Serum sickness
Thrombotic venous/arterial occlusion
Stroke
Hypotension

Wernicke's Encephalopathy- non alcoholic causes

prolonged intravenous feeding,

hyperemesis gravidarum, 

anorexia nervosa, 

refeeding after starvation, 

thyrotoxicosis, 

regional enteritis, 

malabsorption syndromes, 

hemodialysis, 

peritoneal dialysis,

uremia, 

HIV,

malignancy, and 
gastroplasty with postoperative vomiting

Hughes GBS Disability Scale

Guillain-Barré Syndrome Disability Scale (Hughes)

0	Healthy
1	Minor symptoms or signs of neuropathy but capable of manual work/capable of running
2	Able to walk without support of a stick (5m across an open space) but incapable of manual work/running
3	Able to walk with a stick, appliance or support (5m across an open space)
4	Confined to bed or chair bound
5	Requiring assisted ventilation (for any part of the day or night)
6	Death

Asbury Criteria for GBS

Diagnostic criteria
Assessment of current diagnostic criteria for Guillain-Barre syndrome

Required features

• Progressive weakness in both arms and legs
• Areflexia (or hyporeflexia).

Features supportive of diagnosis

• Progression of symptoms over days to 4 weeks
• Relative symmetry
• Mild sensory signs or symptoms
• Cranial nerve involvement, especially bilateral facial weakness
• Recovery beginning 2 to 4 weeks after progression ceases
• Autonomic dysfunction
• Absence of fever at onset
• Typical CSF (albuminocytologic dissociation)
• EMG/nerve conduction studies (characteristic signs of a demyelinating process in the peripheral nerves)

Features casting doubt on the diagnosis

• Asymmetrical weakness
• Persistent bladder and bowel dysfunction
• Bladder or bowel dysfunction at onset
• >50 mononuclear leukocytes/mm³ or presence of polymorphonuclear leukocytes in CSF
• Distinct sensory level.

Features that rule out the diagnosis

• Hexacarbon abuse
• Abnormal porphyrin metabolism
• Recent diphtheria infection
• Lead intoxication
• Other similar conditions: poliomyelitis, botulism, hysterical paralysis, toxic neuropathy.