Central Demyelinating diseases
Multiple sclerosis is a chronic demyelinating disease with pathology that is disseminated in both time and place ie. lesions at different times and different anatomical locations. Motor lesions are all upper motor neurone or cerebellar and sensory include visual symptoms and signs and areas of loss of sensation or altered sensation.
Time course of disease flare ups and the accumulation of disability is variable
- Primary progressive form in which once started the disease proceeds
- Secondary progressive when the disease that has been present for a time then begins to progress
- Relapsing remitting is where there are further episodes which resolve and improve and then recur 70%
- Fulminant a rapid progression to disability in a short period of time
Damage to the myelin sheaths appears to be an autoimmune response to a myelin based antigen. There is increasing evidence that there is also axonal damage. Plaques come on over hours and days with associated symptoms and signs. There is Inflammation and oedema and myelin destruction which over time settles but leaves behind some residual scarring and some symptoms and signs which accumulate with time. Neurological symptoms and signs may persist causing disability and loss of function. Imaging shows white matter rather than grey matter is affected. Plaques are seen in the cervical cord, brainstem, cerebellum, corpus callosum and periventricular areas.
It is very much a young person's disease and patients tend to be typically 20-40 years old, Females > males. HLA DR2 commoner. It is commoner in identical than fraternal twins which suggests a genetic component, It is commoner in northern latitudes and those who move acquire local risk. There has been much discussion about sunlight exposure and vitamin D but no direct link as yet.
- Optic nerve - Optic neuritis (swelling of disc) or retrobulbar neuritis (disc normal) - altered monocular vision/blindness, eye pain especially with movement, red inflamed disc which later becomes pale except if lesion is retrobulbar. Colour vision becomes greyish. Resolves over 4-6 weeks. Established case look for asymmetrical optic pallor
- Cerebellum - ataxia, nystagmus, past pointing, dysdiadochokinesis
- Brainstem and connections - Diplopia, swallowing difficulties, facial numbness and trigeminal neuralgia type picture (V), facial weakness(VII) Dysarthria and dysphagia (IX,X) Motor deficits, sensory deficits in any limb, Internuclear ophthalmoplegia from medial longitudinal fasciculus (One Eye abducts but no adduction in other)
- Periventricular white matter and other white matter bundles - regional sensory loss and upper motor neurone, Corpus callosum
- Cervical and thoracic cord - spastic paraparesis (see cord section) and Lhermitte's sign - neck flexion gives electric shock pain. Transverse myelitis may cause arm (cervical cord) , leg weakness, sensory level, bowel and bladder disturbance and sexual dysfunction
Signs and symptoms disseminated in time and anatomical location. Symptoms often worsened with heat - Uthoff's phenomenon e.g. unable to get out of hot bath and avoid hot climates for holidays. Fatigue can be debilitating but look for other causes e.g. anaemia, thyroid disease.
CT may show periventricular atrophy. However MRI T2 weighted and FLAIR sequence images are the modalities if choice and may show lesions with the most common affected sites being the periventricular white matter, corpus callosum, brainstem and spinal cord. White matter lesions perpendicular to the ventricles are called "Dawson fingers" .On T1 images the lesions appears as "black holes" and correlate more with clinical severity. Lesions may also be seen in the cord typically at cervical level. In older patients T2 periventricular lesions may be due to vascular disease and care with diagnosis must be taken. Other tests done much less so now include Visually evoked responses which demonstrate delayed due to poor conduction from demyelination. Still in use is CSF examination for oligoclonal bands (non specific and raised lymphocytes 10-25 cells/mm. If Cell counts > 100 consider ADEM or Devic's disease. Negative CSF may suggest an alternative diagnosis.
Management of MS is team based with specialist neurologists supported with specialist nurses and access to neurorehabilitation and close liaison with the general practitioner. Education and counselling are important. Many patients with MS lead productive long lives. The young and female do statistically better.
Expert support to manage spasticity, fatigue, bladder, bowels with a Multidisciplinary approach in the community and local social services. May need adaptation to the house and access to simple motility aids such as stick, frame or wheelchairs and other aids to help. Cars can be adapted. Psychological and nursing support. Hyperreflexic bladder - may use reflex emptying or intermittent catheterisation. Intention tremor may be helped with Isoniazid. Respite care should be available. Manage Spasticity - Baclofen, Tizanidine, Gabapentin, Botulinum. Support the carers who are often spouses or even parents.
Acute flare ups can be managed with a short spell of hospitalisation and IV Methylprednisolone over 3 days shorten flare ups but no benefit long term and repeated courses for flare ups not always encouraged as rare and dangerous side effects have been reported.
Disease modifying treatments are Interferon Beta-1a, Interferon Beta - 1b, Glatiramer acetate. They can reduce relapses in ambulatory patients with relapsing remitting disease but are expensive and so there are strict criteria for usage. Neutralising antibodies can form.
Acute Disseminated Encephalomyelitis (ADEM)
ADEM causes an acute episode of intense inflammation of the brain and/or spinal cord leading to areas of central demyelination and has a mortality of 2%. It can affect infants, children and adults. Incidence has fallen with the use of vaccination for childhood illnesses e.g. MMR. In the past it was associated with Smallpox vaccination. ADEM is commoner in children than adults. Unlike MS it is a monophasic illness. It may be post infectious. There may be preceding illness such as measles, mumps, rubella, mycoplasma, EBV, influenza, VZ or smallpox immunisation.
Pathology of ADEM shows perivenular round cell inflammation and there may be haemorrhage. CSF myelin basic protein concentration, reflecting demyelination, is frequently elevated but is non specific
Clinically the patient has an "Encephalitis" with fever, fatigue, headache, nausea and vomiting, coma, neck stiffness, seizures. There may be additional localising signs and symptoms e.g. hemiparesis, ataxia, bilateral optic neuritis, transverse myelitis.
MRI scan may show multiple lesions of the same age representing inflammation and demyelination in brain and or cord. There may be cerebral oedema and areas of haemorrhage. CSF analysis should be undertaken to exclude differentials (HSV encephalitis). Usually the CSF < 100 white cells but may be normal (if higher ensure you have excluded infective cause before giving steroids and add aciclovir and get senior advice). The CSF immune profile remains normal despite recurrences (unlike MS)
Management is intravenous methylprednisolone and response can be marked. Also consider plasmapheresis or intravenous immunoglobulin therapy. Patient will need physical therapy and Occupational therapy and neurorehabilitation which all need to be considered.
Neuromyelitis Optica (Devic's disease)
Investigations include MRI Brain and cord which should show cord lesions over several levels. There are delayed evoked potentials and CSF shows elevated cell count. There are antibodies to aquaporin 4 antigen. Management is with high dose IV methylprednisolone or plasmapharesis (which always suggests an antibody mediated disease)
Progressive multifocal leukoencephalopathy (PML)
Clinically there is progressive paralysis, hemiparesis, delirium and visual loss. Investigations include FBC, U&E, HIV test - low CD4 count and a CSF PCR for JC virus. MRI shows subcortical lesions seen on T2 weighted images.
Management is better for those with AIDS as the disease may stabilise with HAART. Stop any immune suppressant if possible. The overall prognosis is poor. Cytarabine has been used with mixed results