Neurology: Day 3-10

Time for a bit of a catch-up!

So I'm still on Outpatient Neurology. This rotation works in an interesting way - we switch between different Attendings every day. This works out really well because each attending has one area of neurology which he/she specializes in, ranging from Movement Disorder Specialists (where you see a lot of Parkinson's patients and tremors and in theory at least Huntington's Chorea and so on), Headache Specialists (Migraine with or without aura, Tension Headaches, or Cluster Headaches), Seizures Specilaist (Simple/Complex Partial/Generalized and all of their subcategories), Demyelinating Disease Specialists (Multiple Sclerosis), Stroke Specialists, Neurosurgeons, Pain Management, and Neuropathy Specialists (Diabetes, Chemotherapy-induced, etc). This has been such an asset for us as students, as we get the opportunity to work directly with the people who know the most about each specific neurological disease. It also makes it difficult for us, as we are working directly with very specific problems which require an incredibly large depth of knowledge in one area - as third year medical students, we have a vast breadth of knowledge, but our depth is something which will be much more developed during the residency years.



As I had blogged about Migraines and Headaches previously, which are the most common neurological complaint encountered, today I decided to go into a little more depth regarding Multiple Sclerosis.

Left: T2-weighted MRI of Brain - Demyelinated plaques periventricularly

Right: Flair MRI of Brain - Demyelinated plaques (white spots) periventricularly

*MS cannot be diagnosed purely upon radiographs; Gliomas might present in a similar fashion.

*MUST be Correlated to Clinical Features to Diagnose*

Multiple Sclerosis (MS) is a selective demyelination of the CNS, with multifocal zones of demyelination scattered throughout white matter - The classic location is at the angles of the lateral ventricles. The demyelination occurs in the white matter of the brain and spinal cord and tends to spare the grey matter/axons and the PNS. Common tracts involved: pyramidal, cereballar, medial longitudinal fasciculus, optic nerve, and posterior columns.

Women are 2-3times more likely to have MS than men. The etiology is unknown, but is probably secondary to the interplay between environment, immunological, and genetic factors.

Clinical Correlation: Let me tell you a little bit about a very kind young woman I had the opportunity to spend some time with in the clinic. She is in her mid-40s. She first noticed some tingling (paresthesia) in her right hand when she was in her young 20s, and over time she also developed some weakness in her right leg. She stated that she has been constipated (dysautonomia) since as far back as she can remember. But what drew her to visit her physician was when she developed episodes of double vision (diplopia) when she was in her late 20s/early 30s. At this clinic visit, she had many complaints relating to her diagnosis of MS: weakness in right side, tingling in her right hand, some difficulty in walking, fatigue causing her to sleep over 12 hours per day, constipation, depression, anxiety, complaints from her husband that "she isn't the same person I married; she's a completely different person to the one I fell in love with" (personality changes), inattentiveness, softening of voice (laryngeal muscles exhibiting weakness) and a recent episode of exquisitely painful Trigeminal Neuralgia. At the last visit to the clinic, she began taking Recombinant Interferon Beta-1b, which she states has helped improve some of her symptoms, in particular those of constipation, trigeminal neuralgia, less fatigue, and less anxiety and depression. She was seen in the clinic for a follow-up of her current medication regimen, to assess for any adverse effects, and to re-evaluate her current condition. We kept her on full dose of the Interferon beta-1b and to follow up with us again in 2 months or sooner if her condition changes.

Clinical Features of MS:

1. Transient sensory deficits (most common initial presentation); often described as a decrease in sensation or paresthesias in the upper and lower limbs.
2. Fatigue (one of the most common complaints)
3. Motor Symptoms, mainly weakness or spasticity which may appear insidiously or acutely. The cause is involvement of the pyramidal tract.
1. Spasticity can impair ability to walk or balance
2. Can lead to paraparesis, hemiparesis, or quadriparesis
4. Visual Disturbances: OPTIC NEURITIS
1. Monocular visual loss (in 20% patients) 
2. Pain on movement of eyes
3. Central Scotoma
4. Decreased pupillary reaction to light
5. Visual Disturbances: INTERNUCLEAR OPHTHALMOPLEGIA - strongly suggestive of MS
1. A lesion in the Medial Longitudinal Fasciculus --> ipsilateral medial rectus palsy on attempted lateral gaze (adduction defect) and horizontal nystagmus of abducting eye (contralateral to side of lesion)
2. May cause Diplopia
6. Cerebellar Involvement:
1. Ataxia, Intention tremor, dysarthria
7. Loss of bladder control 
1. Due to upper motor neuron injury in spinal canal
8. Autonomic Dysfunction
1. May present as impotence and/or constipation
9. Cerebral Involvement
1. In advanced illness: anxiety, depression, personality change, and emotional lability
10. Neuropathic Pain
1. Hyperesthesias and Trigeminal Neuralgia

Course:

1. Initially present during 20s-30s with a localizing defect, such as optic neuritis/one-sided weakness/numbness.
2. Variants of MS:
1. Clinically Silent: "Stable" or "Benign" MS. Some may progress late in the course
2. Relapsing/Remitting: Most Common. Exacerbations followed by remissions
3. Secondary Progressive: Relapsing/remitting disease with gradual worsening of symptoms that is progressive in later years.
4. Primary Progressive: Steady, progressive disease that appears later in life (after 40 years of age), and tends to have less visual and more axial involvement.
3. Attacks average around once per year.
4. Highly variable prognosis, with a normal life span in most patients.
1. Diminished quality of life, although many will never develop debilitating disease
2. Around 1/3 patients eventually progress to severe disability
3. Factors which increase risk of progression to severe disability:
1. Frequent attacks early in the disease course
2. Onset at an older age
3. Progressive course
4. Early cerebellar or pyramidal involvement

Diagnosing MS: Essentially a Clinical Diagnosis:

• 2 episodes of symptoms; Evidence of 2 white matter lesions (clinically or on imaging)
• Lab-supporting evidence: Two episodes of symptoms, evidence of at least 1 white matter lesion on MRI, and abnormal CSF (oligoclonal bands in CSF)
• Probable MS: Two episodes of symptoms and either one white matter lesion or oligoclonal bands in CSF.

Treating MS:

1. Treatment of severe attacks:
1. High-dose IV corticosteroids can shorten an acute attack, but does not prevent progression.
2. Most acute attacks will resolve within 6 weeks with or without treatment.
2. Disease-Modifying Therapy:
1. Interferon Therapy:
1. Recombinant interferon beta-1a, Recombinant interferon beta-1b, and glatiramer acetate
1. Shown to reduce relapse rates in 37%, 33%, and 29%, respectively.
2. Nonspecific immunosuppression (cyclophosphamide) if rapidly progressive disease
3. Symptomatic Therapy:
1. Baclofen for muscle spasticity
2. Carbamazepine or Gabapentin for neuropathic pain

References: 

StepUp to Medicine, Second Edition. Agabegi, Agabegi. Lippincott, Williams & Wilkins. 2008.

Casefiles for Neurology. Toy, Simpsom, Pleitez, Rosenfield, Tintner. Lange. 2008.

http://www.imaginis.com/multiple-sclerosis-symptoms-diagnosis/magnetic-resonance-imaging-is-the-method-of-choice-for-imaging-ms-plaques-in-the-brain