Tuesday, November 13, 2012

Retinal Vasculitis with CNS disease

In a patient with retinal vasculitis, it is useful to know the following:
1) Type of retinal vessels involved - arterioles, venules, capillaries
2) CSF study normal or abnormal
3) MRI Brain normal, vasculitis, white matter changes, ventricular enlargement


Identification of retinal vessels involved 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855661/
Retinal vasculitis affecting predominantly the veins (phlebitis) has been described in association with Behçet's disease, tuberculosis, sarcoidosis, multiple sclerosis, pars planitis, retinal vasculitis associated with tuberculoprotein hypersensitivity (Eales' disease), human immunodeficiency virus infection (HIV). Retinal arteritis is more commonly seen in acute retinal necrosis, idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and systemic vasculitides such as SLE, polyarteritis nodosa, and Wegener's granulomatosis, Churg-Strauss syndrome and cryoglobulinemia.

List of causes of retinal vasculitis (Uptodate)


Systemic disorders
Behcet's disease
Granulomatosis with polyangiitis (Wegener's)
Sarcoidosis
Relapsing polychondritis
Systemic lupus erythematosus
Giant cell arteritis
Polyarteritis nodosa
Multiple sclerosis
Whipple's disease
Crohn's disease
HLA-B27 associated conditions



Infectious disorders
Toxoplasmosis
Tuberculosis
Syphilis
Herpes simplex
Herpes zoster
Acute retinal necrosis
Cytomegalovirus
Coccidiomycosis
Hepatitis
Amoebiasis
Candidiasis
Leptospirosis
Ricketsia
Brucellosis
Lyme disease
Human immunodeficiency virus
Toxocariasis



Ocular disorders
Birdshot retinochoroidopathy
Pars planitis
Eale's disease
Retinal arteriolitis
Behcet's sine systemic disease
Sympathetic ophthalmia




Classification of retinal vasculitis by involved vessel
Disease
Primary vessel involved
Polyarteritis nodosa
Muscular arteries
Granulomatosis with polyangiitis (Wegener's); giant cell arteritis
Medium to small arteries
Systemic lupus erythematosus
Small arteries
Whipple's disease
Capillaries
Behcet's disease; sarcoidosis; multiple sclerosis
Veins
Crohn's disease; relapsing polychondritis
Arteries and veins
HLA-B27 associated conditions, such as ankylosing spondylitis
Variable or no involvement


Tuesday, November 6, 2012

EEG Questions

What is the electrical principle behind an EEG?

What is actually moving (?electrons), why is it moving, and how do we pick up the amount and direction of movement?

What is the relation between movement of electrons and electrical field?

What are the electrodes on the surface of the scalp actually picking up?

How is the electric field in scalp recording different from ECG?

What is really meant by potential difference?

Saturday, August 25, 2012

Types of diabetic neuropathies

Symmetric
  • Distal symmetric polyneuropathy.
  • Autonomic neuropathy.
  • Transient distal sensory neuropathy.
  • Diabetic neuropathic cachexia (rare).
Asymmetric
  • Diabetic amyotrophy (proximal diabetic neuropathy, diabetic lumbosacral radiculoplexopathy).
  • Cranial neuropathy.
  • Truncal radiculopathy.
  • Isolated mononeuropathy.

Observations on role of IVIg in diabetic neuropathy

Acta Myol. 2003 Dec;22(3):97-103.
Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome.
Engel WK.

Abstract

Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes.

Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.

Diabetic Neuropathy

Multifocal acquired demyelinating sensory and m... [Muscle Nerve. 1999] - PubMed - NCBI

Multifocal acquired demyelinating sensory and m... [Muscle Nerve. 1999] - PubMed - NCBI
Saperstein, D. S., Amato, A. A., Wolfe, G. I., Katz, J. S., Nations, S. P., Jackson, C. E., Bryan, W. W., Burns, D. K. and Barohn, R. J. (1999), Multifocal acquired demyelinating sensory and motor neuropathy: The Lewis–Sumner syndrome. Muscle Nerve, 22: 560–566.
We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.
'via Blog this'

Chronic Immune Demyelinating Neuropathies: Variants

http://neuromuscular.wustl.edu/antibody/pnimdem.html#variant


Acute onset
β-Tubulin antibodies
Childhood
CNS features
Diabetes
IgM vs GM2 & GalNAc-GD1a
Motor
M-protein: IgM; IgG or IgA
Multifocal
Upper limb
Perineuritis
POEMS
Sensory
Subacute
Typical


  • Multifocal CIDP9
    • Nosology
    • Age range: 28 to 58 years
    • Weakness
      • Asymmetric
      • Distal > Proximal
      • Arms > Legs (78%)
      • Proximal syndrome: Occasional
        • Phrenic nerve: Diphragm weakness; Respiratory insufficiency
        • Suprascapular nerve: Infraspinatus ± Supraspinatus weakness
        • Other scattered distal & proximal muscles
    • Sensory loss: Distal; Pansensory; Rarely severe or disabling
    • Tendon reflexes: Focal loss
    • Course: Slowly progressive, or Relapsing-Remitting
    • Laboratory
      • Electrophysiology
        • Multifocal conduction block
        • Nerve conduction velocities: Variably slow
        • Distal latencies: Variably prolonged
      • CSF protein: High but usually < 100 mg/dL
      • IgM anti-GM1 antibodies: Never
      • MRI: Swollen nerves in brachial plexus with high T2 signal
      • Nerve pathology
    • Treatment: PrednisoneHIG

  • Multifocal upper limb CIDP2,6
    • Male:Female = 1.9:1
    • Onset
      • Mean = 43 to 54 years; Range 9 to 75 years
      • Rarely childhood
      • Acute or Progressive
      • Distal
    • Clinical
      • Weakness
        • Onset: May be motor, sensory, or both; With reduced pain
        • Single or multiple upper extremity nerves
        • Distal > Proximal
        • Asymmetric > Symmetric
        • Monomelic or Bilateral
      • Sensory
        • Paresthesias or numbness early in most
        • Pain: 22%; Often localized to peripheral nerve territory
        • Sensory loss: Usually mild, distal; Often asymmetric
      • Tendon reflexes: Often reduced in involved limb(s)
      • Course
        • Progressive: To legs in 25%
        • Some stabilize or spontaneously resolve
      • Cranial nerves: 17%; Optic; III; VII
      • Rule out: Brachial neuritis
    • Laboratory
      • Anti-GM1 ganglioside antibodies: Uncommon
      • CSF protein
        • High in 40% to 72%
        • Mean 64 mg/dL; Range 21 to 128
      • Nerve conduction studies
        • Conduction block (100%): Proximal or Distal segments
        • Slowing 35%;
        • CMAP amplitude: Reduced (56%)
        • Abnormal SNAPs: Some patients; Up to 83%
        • Leg involvement: 34%
      • MRI
        • Usually normal
        • May have brachial plexus lesions
    • Treatment
      • Response to Prednisone or HIG in some (> 50%)
      • Often less recovery than with generalized CIDP

  • Motor predominant CIDP 36
    • Clinical
      • Onset
        • Age: 8 to 24 years
        • Weakness: Progressive over 1 to 6 months
      • Weakness
        • Distal > Proximal
        • Symmetric
        • Arm predominant or Arms & Legs
        • May be exacerbated by heat (Uhthoff-like phenomenon)
      • Sensory exam: Normal
      • Tendon reflexes: Diffusely absent
    • Laboratory
      • Nerve conduction studies
        • Motor: Distal & F-wave latency long; Conduction block; NCV slowed (17 to 33 M/s
        • Sensory: Normal or reduced SNAP amplitudes
      • CSF: Protein high
      • GM1 antibodies: Not present
    • Differential diagnosis: Multifocal motor neuropathy

  • Sensory CIDP
    • Clinical
      • Sensory
        • Loss: Distal predominant; Pansensory or Small fiber
        • Pain
      • Motor: Normal or minimal distal weakness
      • Tendon reflexes: Normal or Reduced
    • Electrophysiology (NCV): Motor & Sensory demyelination
      • Motor
        • Conduction block
        • NCV: Slow
        • Distal latency: Long
      • Sensory: Slow NCV
    • Treatment: Poor response to prednisone or HIG

  • Childhood CIDP
    • Prevalence: ~ 1 in 300,000; Male > Female
    • Preceding infections or vaccinations: 54%
    • Onset: Childhood to Teens; Rarely infancy
    • Course: Several patterns
      • Monophasic: 25%
        • Peak disability < 3 months
        • Off medications in < 1 year
      • Chronic
        • Persistent weakness & disability
        • Require continued immunosuppression
      • Acute onset: 25%
      • Relapsing: Often treatment related
    • Clinical patterns
      • Overall
      • Weakness: Proximal + Distal; Usually symmetric
      • Sensory loss: Pansensory; Distal; Symmetric
      • Tendon reflexes: Reduced or Absent
      • Other: Rare clinical CNS features
    • Disease Associations
      • Comparison with adult CIDP: Less with M-proteins & Diabetes
      • CNS changes: Rarely reported19
      • Other systems: Renal; Hearing28
    • Prognosis
      • Better for remission with relatively rapid onset
      • Worse: Axonal loss
    • Laboratory
      • Pathology
        • Similar to adult CIDP
        • Chronic cases may have prominent demyelinating features
      • MRI: Gadolinium enhancement of roots very common; Occasional CNS changes
      • Nerve conduction: Similar to adult CIDP
    • Treatment
      • Corticosteroids: Response in > 90%
      • IVIg: Response in > 80%
      • Methotrexate: 2nd line treatment

  • CIDP + IgM M-protein vs β-tubulin
    • Weakness: Slowly progressive; Asymmetric
    • Hyporeflexia
    • Poor response to prednisone
    • Antigenic epitope: β-tubulin amino acids 301-314

  • CIDP associated with IgG or IgA M-protein
    • Similar clinical syndrome to typical CIDP
    • Weakness: Slowly progressive; Symmetric
    • Partial response to immunotherapy

  • CIDP + Diabetes mellitus8
    • Patient characteristics: Most similar to CIDP alone
    • Differences from CIDP
      • Age: Older (67 years)
      • Symptoms: More gait imbalance
      • Electrodiagnostic: More axonal loss
      • Treatment: Less improvement

  • CIDP: Acute onset32
    • Onset: Progressive over days to weeks
    • Clinical
      • Weakness
        • Symmetric
        • Proximal & Distal
        • Uncommon: Face, Tongue, Eye movements, Respiratory failure
        • Less severe than GBS
      • Sensory loss: Distal
      • Tendon reflexes: Reduced
      • Course
        • Slower progression to nadir than GBS
        • Partial, but not complete improvement in strength over months
        • Treatment related exacerbations
          • Common
          • Time of first exacerbation: Median 18 days; Range 10 to 54 days
          • Especially > 8 weeks after onset
          • May occur ≥ 3 times
    • Laboratory
      • Electrodiagnostic
        • Prominent demyelinating features early in disease course
        • More slowing of motor nerve conduction velocity than GBS
        • Conduction block (30%)
        • EMG denervation (75%)
      • CSF protein: High
      • Antibodies: IgG anti-glycolipid uncommon

  • CIDP: Subacute onset23
    • Male > Female: 2 to 1
    • Onset
      • Age: Childhood or Adult
      • Progressive over 4 to 8 weeks
      • Antecedent infection (38%)
    • Clinical
      • Weakness (80%)
        • Symmetric (90%)
        • Proximal & Distal
      • Sensory loss (80%): Distal
      • Tendon reflexes: Reduced
      • Course
        • Improvement with corticosteroid treatment
        • Few relapses
    • Laboratory
      • Electrodiagnostic: Demyelination
        • NCV: Slow
        • Terminal latency: Prolonged (50%)
        • Conduction block: 50%
        • Temporal dispersion: 50%
        • Sensory: Absent SNAPs
      • CSF protein: High
      • Nerve biopsy
        • Demyelination in some: May require teased fibers to document
        • Inflammation: Epineurial; Some patients

  • CIDP + CNS features19
    • Frequency: Rare patients with CNS features
    • Onset
    • CNS features
      • Ocular
        • Papilledema: Associated with high CSF protein
        • Visual loss: Optic atrophy
      • Myelopathy
        • Tendon reflexes may be brisk
        • r/o Spinal cord compression from enlarged nerve roots
      • Ataxia
      • Focal CNS myelin loss: 1 patient
        • CNS: Focal mass-like lesion
        • Weakness: Mild; Distal
        • Sensory loss: Mild vibration
        • Tendon reflexes: Normal
        • NCV: Slow; Long distal latency
      • Multiple sclerosis + CIDP27
        • MS duration at onset: 4 to 22 years
        • Clinical
          • Weakness: Distal > Proximal;
          • Sensory loss: Distal; Pan-modal
          • Tendon reflexes: Reduced or Absent
        • CSF protein: > 120 mg/dL
        • Nerve conduction studies: Demyelinating neuropathy
        • Treatment: IVIg; Corticosteroids
    • Rule out: Late onset dysmyelination (MLDKrabbe)
    • Treatment: Corticosteroids
  • Perineuritis
    • Usually axonal neuropathy: Occcasional demyelinating neuropathy reported

Lacunar Syndromes

http://en.wikipedia.org/wiki/Lacunar_stroke


Charles Miller Fisher cadaver dissections 1965 publication in Neurology
200-800 micrometer penetrating arteries (?ref)
25% of all ischemic (?ref)
Location (?ref)
  1. Putamen 37%
  2. Thalamus 14%
  3. Caudate 10%
  4. Pons 16%
  5. Capsule posterior limb 10%
The two proposed mechanisms are microatheroma and lipohyalinosis. At the beginning, lipohyalinosis was thought to be the main small vessel pathology, but microatheroma now is thought to be the most common mechanism of arterial occlusion (or stenosis). 

Each of the 5 classical lacunar syndromes has a relatively distinct symptom complex. Symptoms may occur suddenly, progressively, or in a fluctuating (e.g., the capsular warning syndrome) manner. Occasionally, cortical infarcts and intracranial hemorrhages can mimic lacunar infarcts, but true cortical infarct signs (such as aphasia, neglect, and visual field defects) are always absent.

NameLocation of infarctPresentation
Pure motor stroke/hemiparesis (most common lacunar syndrome: 33-50%)posterior limb of the internal capsule,basis pontis, corona radiataIt is marked by hemiparesis or hemiplegia that typically affects the face, arm, or leg of one side. Dysarthriadysphagia, and transient sensory symptoms may also be present.
Ataxic hemiparesis (second most frequent lacunar syndrome)posterior limb of the internal capsule,basis pontis, and corona radiata, red nucleus, lentiform nucleus, SCA infarcts, ACA infarctsIt displays a combination of cerebellar and motor symptoms, including weakness and clumsiness, on the ipsilateral side of the body. It usually affects the leg more than it does the arm; hence, it is known also as homolateral ataxia and crural paresis. The onset of symptoms is often over hours or days.
Dysarthria/clumsy hand (sometimes considered a variant of ataxic hemiparesis, but usually still is classified as a separate lacunar syndrome)basis pontis, anterior limb or genu of internal capsule, corona radiata, basal ganglia, thalamus, cerebral peduncleThe main symptoms are dysarthria and clumsiness (i.e., weakness) of the hand, which often are most prominent when the patient is writing.
Pure sensory strokecontralateral thalamus (VPL), internal capsule, corona radiata, midbrainMarked by persistent or transient numbness, tingling, pain, burning, or another unpleasant sensation on one side of the body.
Mixed sensorimotor strokethalamus and adjacent posteriorinternal capsule, lateral ponsThis lacunar syndrome involves hemiparesis or hemiplegia with ipsilateral sensory impairment
http://stroke.ahajournals.org/content/38/10/2706.full

The pathophysiological heterogeneity of ischemic stroke may be relevant to the development of acute-phase therapies because it is possible that what works for one subtype of stroke may work differently for another. Although no clinical stroke syndrome is absolutely pure with respect to pathophysiology, lacunar syndromes are the most homogeneous. Lacunar syndromes are usually due to a small subcortical infarct in the territory of a penetrating artery caused by in situ microatheroma or lipohyalinosis. Neurochemical studies suggest that subcortical ischemia may respond differently to hyperacute intervention than cortical ischemia. Subgroup analyses in a trial of a putative neuroprotective agent suggested the possibility of (an unexpected) benefit in patients with lacunar strokes. (Images Trial)

Lacunes by CM Fisher 1965

http://www.neurology.org/content/15/8/774.full.pdf+html?ijkey=0a1309280809bdbe6767730541099e41b1558542&keytype2=tf_ipsecsha

Cadaveric dissections
0.5 to 15mm cavities
Principally in basal ganglia and basis pontis

Why Lacunar Syndromes Are Different and Important


The lacunar hypothesis has been one of the hallmarks of the modern understanding of the clinical categorization of the pathogenesis of stroke. Stated simply, the hypothesis implies that classical lacunar syndromes are caused by small deep brain infarcts, due to occlusion of a single penetrating artery. The underlying pathology has been documented to be either in situ microatheroma or lipohyalinosis, rather than embolism.

The controversy arises because many clinicians remain less than convinced that embolism is not a frequent cause of lacunar infarcts and hence would not warrant a different investigative strategy from other ischemic stroke syndromes. As we see it, the established facts are as follows:

1. There is no animal model of lacunar infarction due to in situ small-vessel disease, in contrast to the embolic model quoted by Futrell.

2. The proportion of embolic sources in patients with lacunar syndromes is substantially lower than for other hemispheric ischemic strokes, as stated by Norrving.

3. MRI studies have demonstrated that variable proportions of patients presenting with classical lacunar syndromes have sometimes shown multiple concurrent infarcts or more widespread perfusion abnormalities suggesting embolism.

4. Other evidence for a possible embolic source in some cases includes a benefit to the subset of patients with lacunar syndromes and ipsilateral high-grade carotid stenosis in the NASCET trial. Further, aortic arch atheroma has been shown to be a risk factor for lacunar stroke.

While recognizing that there is some heterogeneity of mechanism within the lacunar syndromes, we believe that the concept is clinically useful, and that the evidence favors the view that the majority are due to in situ, small-vessel disease. Hence, their recognition enables clinicians to be less aggressive in the search for an embolic source, although we would suggest that exclusion of large-vessel disease and cardiac screening is appropriate. Further, there are compelling clinical and epidemiological reasons to separate lacunar from nonlacunar ischemic strokes. For example, their outcome is substantially more favorable and their location in deep white matter may have implications for therapy. Intriguingly, in the recently reported IMAGES trial, a planned subanalysis showed an unexpected benefit for lacunar syndromes. We encourage further trials of therapy within this group such as the current SPS3 trial of combined antiplatelet and blood pressure lowering therapy. It may well be that the therapeutic response in lacunar infarcts may be somewhat different than in predominantly gray matter infarcts, given the well-known differences in ischemic neurochemical cascades.

Given the importance of small-vessel disease, particularly in Asian countries, and its relationship to both clinical stroke and cognitive decline, we strongly believe that this disease entity deserves specific recognition to focus future research initiatives. While embolism is the likely cause of a minority of lacunar infarcts, we do not see it as the key, but perhaps a small component of a combination lock.

Images Trial
Lancet. 2004 Feb 7;363(9407):439-45.
Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial.
Muir KW, Lees KR, Ford I, Davis S; Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators.

BACKGROUND: Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days.

METHODS: 2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done.

FINDINGS: The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group.

INTERPRETATION: Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.

Editorial Comment: The Fall and Rise of Lacunar Infarction With Carotid Stenosis

Editorial Comment: The Fall and Rise of Lacunar Infarction With Carotid Stenosis


Comment on
Tejada J, Díez-Tejedor E, Hernández-Echebarría L, Balboa O. Does a relationship exist between carotid stenosis and lacunar infarction? Stroke.2003; 34: 1404–1409.



In this issue of Stroke, Tejada et al address the potential relationship between LI and the presence of an internal carotid artery stenosis (ICAS). The article investigates the relationship between LI and ICAS in a large prospective study of 330 patients, including 205 with LI and 125 with NLI. 


The authors draw 4 interesting conclusions: First, even if the presence of significant (>50%) ICAS is lower in LI compared with NLI, the probability of carotid disease increases when LI is present in the ipsilateral carotid territory. Second, ICAS without contralateral ICAS was reported in 73% of the cases, suggesting that ICAS is indeed a marker of ipsilateral LI. Third, logistic regression analysis in “pure” LI associated with ICAS >50% showed that peripheral artery disease was the only significant factor associated with stroke. Fourth, the combined presence of a left ventricular hypertrophy (LVH) with ICAS >70% determined predominance of LI in 1 hemisphere, suggesting a role of ICAS. Multivariate analysis showed that only 2 factors predicted unilateral LI:LVH and ICAS >75%. Tejada et al conclude that moderate ICAS may appear in an appreciable percentage of LI in the ipsilateral territory and that severe ICAS is related to multiple LI. 


The main message of the report is the identification of the need to search for large-artery disease as the cause of LI. The question raised is whether the etiological association between ICAS and LI should be accepted as a final evidence. 

The study of Tejada et al presents some limitations: 

First, authors used only clinical examination and CT scan (not MRI) to diagnose LI. Cortical small infarcts may mimic LI and inversely, so that MRI with DWI is currently the “gold standard” to investigate an isolated and “active” lacune. Second, because of possible differences between the 2 centers for grading the degree of ICAS, it is reasonable to assume that some ipsilateral or contralateral ICA stenoses were overestimated. Indeed, only 34.5% of cases had radiological examination (DSA or MRA) to confirm ultrasound. In this series, 73% of ipsilateral ICAS were not associated with contralateral ICAS, which is very high. The problem is that criteria to grade ICAS and the technique used, either DSA or ultrasound or MRA, limit the comparisons with other studies. Third, as seen in the article’s Tables 1 and 3, there are no precise data on potential cardiac sources of embolism and the type of echocardiography used. Moreover, as the neuroimaging used to diagnose LI was CT scan, some LI located in the brainstem may have been considered as hemispheric LI ipsilateral to ICAS. 


Tuesday, August 7, 2012

Medial Medullary Syndrome Practical Aspects

Medial Medullary Syndrome: Report of 18 New Patients and a Review of the Literature. Jong Sung Kim, Hyeon Gak Kim, Chin Sang Chung. Stroke. 1995;26:1548-1552
-----------------------
Abstract
Background and Purpose With advanced imaging techniques, infarctions occurring in the medulla are now more easily identified. To date, however, only approximately 30 cases of medial medullary infarction syndrome (MMS) have been reported, and the clinical and radiological characteristics of MMS remain to be studied.
Methods We studied 18 patients (15 men, 3 women; mean age, 62 years) who had compatible clinical and MRI findings of MMS and reviewed the previously reported cases.
Results Seventeen patients had a unilateral lesion usually involving the upper medulla, and 1 had bilateral lesions. Fifteen patients had unilateral sensorimotor stroke, while 2 presented with pure motor stroke. The face was usually but not always spared. The degree of hemiparesis varied, and a tingling sensation with decreased vibration and position sense was the most common sensory manifestation. Two patients had lingual paresis, and none suffered respiratory difficulties. One patient presented with bilateral gait ataxia without sensorimotor dysfunction. Angiography or MR angiography performed in 9 patients showed vertebral artery disease in 6. Three patients had concurrent lateral medullary infarction, and 1 had a previous history of lateral medullary syndrome. The prognosis was generally good, although residual hemiparesis remained in patients with initially severe hemiparesis. Review of 26 previously reported cases showed that they frequently had bilateral lesions, often presenting with quadriplegia, lingual paresis, respiratory symptoms, and a grave prognosis.
Conclusions Our data illustrate that MMS is most often manifested as benign hemisensorimotor stroke frequently associated with tingling sensation and impaired deep sensation. This benign form of MMS should be much more common than MMS with poor prognosis and may have been frequently misdiagnosed as capsular or pontine stroke before the era of MRI. 
----------------------
A few clinical details
Hemiparesis was the most common clinical manifestation of MMS; 15 had contralateral hemiparesis, and 2 (patients 15 and 13) had ipsilateral hemiparesis and crural monoparesis, respectively. One (patient 12) did not have motor weakness but had transient bilateral gait ataxia. In 2 (patients 5 and 14), motor weakness was the only clinical manifestation (pure motor stroke), although patient 5 had slight residual sensory symptoms due to previous LMS. At the peak of the weakness, the degree of the hemiparesis (motor power of the proximal limbs) was severe (0 to 2 on a scale of 5) in 3, moderate (3 on a scale of 5) in 5, and mild (4 or clumsiness on a scale of 5) in 9. Generally, the distal part of the limb (hand and foot) was more severely affected compared with the proximal part. In patients with significant motor deficit, the progression of weakness usually evolved for several hours or days. During this progression, muscle tone was generally flaccid but became spastic during the recovery phase.
Hemisensory symptoms were the second most common clinical manifestation, occurring in 15 patients (including 3 with LMS). Initially, 12 patients felt tingling or a numb sensation. The face was usually spared, but the area of paresthesia occasionally ascended to the periotic area (patients 3 and 11) or even to the midface (patients 9, 16, 17, and 18). Vibration sense was impaired in 14 patients, and decreased position sense was noted in 10. However, only 1 (patient 16) had severely decreased position sense, and none described the vibration sense as reduced more than 50% of the intact side. Seven patients without LMS stated that the pinprick sense was also mildly impaired.
Headache (3 cases) and nausea/vomiting (3 cases) were uncommon, and dizziness/ vertigo was noted in 9 patients. One (patient 18) had transient ipsilateral lingual paresis, and patient 3 showed clumsy tongue movements bilaterally. Including these 2 patients, 4 without LMS had dysarthria, while 2 (patients 2 and 18) had dysphagia. Mild facial paresis was noted in 4 patients. None had respiratory disturbances. One had horizontal nystagmus, 1 had upbeat nystagmus, and 1 had both. Patient 16 had transient gaze paresis and long-lasting sixth nerve palsy.
The patients were followed up for 14 days to 41 months (mean, 11 months). None died during the follow-up period. All were able to walk unassisted, although mild residual paresis remained in patients with initially moderate to severe motor weakness. Uncomfortable paresthesia over the palm or foot became the most distressing symptom in some patients (patients 9, 11, 16, and 17). 
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Lingual paresis
Unexpectedly, lingual paresis, described in 12 of 26 cases reported in the literature, was observed in only 2 of our patients, with the lesions extending dorsally. Lingual paresis is caused by lesions extending into the lateral part of the medulla, affecting the fibers of the hypoglossal nerves or fascicles, or lesions extending deep into the hypoglossal nucleus.
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Differences from previous reports
The paucity of lingual paresis and respiratory symptoms along with the patients’ benign outcome was strikingly different from previously described subjects in whom prognosis was generally poor. These differences may be explained in several ways. First and most importantly, the diagnosis of MMS was made by MRI in our patients, whereas that of most of the previously reported cases was based on autopsy. Second, since hypertension seems to be more prevalent and large-vessel atherosclerosis less common in oriental than Western countries, relatively small vessels might have been more often affected in our Korean patients than in previously reported cases. Finally, it may also be possible that the recent progress on risk factor management has led us to encounter more benign cerebrovascular diseases today than before.

Tuesday, July 24, 2012

Movement Disorder Meeting Learning Points

Chennai 22/7/12

  1. Unilateral tongue tremor - PET-CT study of basal ganglionic functions can help
  2. PME's - If valproate is worsening - to consider mitochondrial disorder
  3. Lafora body EEG may show posterior spiking (and giant cortical waveforms on SSEP - stimulus sensitive cortical generators for myoclonus)
  4. Weight gain with valproate would worsen if also given clobazam
  5. Lower limb myoclonus seen in tropical sprue
  6. Lamotrigine described to worsen tics
  7. "End-of-phenotype" - genotype correlations with MRI [discussed by AVS and one more] looked up - the only explanation for the term came from an article - BMC Medical Genetics 2010, 11:114 - Hippocampal and parahippocampal volume reduction is one of the most consistent findings in schizophrenia. Moreover, in a meta-analysis of brain volumes in relatives of patients with schizophrenia, hippocampal reduction was the largest difference between relatives and healthy controls. These findings suggest hippocampal volume as a potential end of phenotype for genetic studies in schizophrenia.
  8. Sea blue histiocytes in generalized dystonia [AVS mentioned] looked up - juvenile dystonic lipidoses with sea blue histiocytes is a variant of Niemann Pick disease type C

Botulinum toxin injection - some practical points

Dr UMS Chennai Workshop on 22/7/12
For Cervical dystonia - torti, lateral, ante, retro
Watch the chin, watch the direction the head takes when the patient is at rest with eyes closed (this will be opposite to the direction where the tremor is maximum), and finally look for asymmetry of muscle hypertrophy. The chin is shifted in torti but not lateralocollis. If torti - needs contralateral SMD + ipsilateral SST complex, if lateral - needs LS, scaleni in addition to trap (?to check for lateral)

Gave inj. to a patient with retro + torti. Identification of SST complex - straight into paraspinal, the toxin will diffuse through to all three muscles. For semispinalis capitis, there is one more inj. point posterior to the insertion of the SMD away from the paraspinal. This is the only muscle here (no overlaps)

For Blepharospasm
Avoid midline (LPS) and give 2 to 3 units at each location, also avoid lower medial canthus (eversion)

For Ankle dorsiflexors (patients with spasticity and toe walking)
Two injections into each head of the gastroc (medial and lateral) and two injections into the middle of the soleus in the center of the bulk

Wednesday, July 18, 2012

Questions regarding seizures

ILAE definition of Seizure:
A seizure is (1) transient (2) occurrence of symptoms and signs (3) due to abnormal enhanced synchronous neuronal activity (4) in the brain

From: Fisher, R. S., Boas, W. v. E., Blume, W., Elger, C., Genton, P., Lee, P. and Engel, J. (2005), Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia, 46: 470–472. 

Discussion:
(1) It has an onset and termination - transient

(2) Clinical manifestations: Seizure presentation depends on location of onset in the brain, patterns of propagation, maturity of the brain, confounding disease processes, sleep–wake cycle, medications, and a variety of other factors. Seizures can affect sensory, motor, and autonomic function; consciousness; emotional state; memory; cognition; or behavior. Not all seizures affect all of these factors, but all influence at least one. In this context, sensory manifestations are taken to include somatosensory, auditory, visual, olfactory, gustatory, and vestibular senses, and also more complex internal sensations consisting of complex perceptual distortions. In previous definitions, these complex internal sensations were referred to as “psychic” manifestations of seizures.

(3) Hughlings Jackson in 1870 provided a now classic definition of an epileptic seizure as a “symptom … an occasional, an excessive and a disorderly discharge of nerve tissue.” By “disorderly,” Jackson probably meant “capable of producing dysfunction,” which is certainly accurate. However, EEG discharges during epileptic seizures are orderly and relatively stereotyped. Firing of neurons may involve inhibition as well as excitation, so it is not always the case that an epileptic seizure involves an excess of excitation over inhibition. A feature more common to epileptic seizures is abnormal enhanced synchrony of neurons.

(4) Definition of an epileptic seizure becomes operationally difficult without ascribing it to the brain. Trigeminal neuralgia, for example, can result from an abnormal enhanced synchrony of neurons in the trigeminal ganglion or the fifth cranial nerve, but would not be considered an epileptic seizure. Neither would hyperactive spinal reflexes resulting in excessive discharge of anterior horns cells and tonic stiffening of a limb. Cerebral cortex is the primary element in the generation of epileptic seizures, but it is not the only one. In some circumstances, epileptic seizures can originate in thalamocortical interactive systems or in the brainstem.

Some further questions to be answered:
1. Why does it have to be 'transient'? Some seizures are fairly prolonged.

Ans: More than transient, what it really implies is that there is a definite onset (change from baseline) and termination (return to baseline activity). That is, there has to be a beginning and an end to this phenomenon.

2. So, is there a situation where we can have abnormal enhanced synchrony that is present from the time of development of brain (no beginning) or persistent abnormal enhanced synchrony (no end)?

Ans:??


3. Why does the abnormal enhanced synchronous activity occur transiently at certain times in certain brains?

Ans: This assumes that there have to be certain provoking factors (time) with neurons that are susceptible (threshold).

4. What are triggering factors versus provoking factors?

Ans: Some seizures are provoked, that is, they occur in the setting of metabolic derangement, drug or alcohol withdrawal, and acute neurologic disorders such as stroke or encephalitis. Such patients are not considered to have epilepsy, because the presumption is that these seizures would not recur in the absence of the provocation. (from Uptodate)

Triggers: Some patients with epilepsy tend to have seizures under particular conditions, and their first seizure may provide a clue to their so-called seizure trigger. Triggers include (but are not limited to) strong emotions, intense exercise, loud music, and flashing lights. Other physiological conditions such as fever, the menstrual period, lack of sleep, and stress can also precipitate seizures, probably by lowering seizure threshold rather than directly causing a seizure. As a result, the temporal relationship to the presenting seizure is often less clear. Triggers may also precipitate nonepileptic paroxysmal disorders, especially syncope.
However, the majority of patients with epilepsy have no identifiable or consistent trigger to their seizures. In addition, triggers are the sole cause of epileptic seizures in only a very small percentage of patients.

4. So, when do we say that someone has epilepsy?
Ans: We can go back to the article cited above. But generally, epilepsy is characterized by recurrent epileptic seizures due to a genetically determined or acquired brain disorder. Approximately 0.5 to 1 percent of the population has epilepsy.

ILAE definition of Epilepsy:
Epilepsy is (1) a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures (2) and by the neurobiologic, cognitive, psychological, and social consequences of this condition. (3) The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Discussion:
(1) The central concept in the definition of epilepsy is an enduring alteration in the brain that increases the likelihood of future seizures. The diagnosis of epilepsy, under this concept, would not require two seizures; it would require only one epileptic seizure in association with an enduring disturbance of the brain capable of giving rise to other seizures. Multiple epileptic seizures due to multiple different causes in the same patient would not be considered to be epilepsy. A single epileptic seizure due to an enduring epileptogenic abnormality would indicate epilepsy, and a single epileptic seizure in a normal brain would not.

(2) At times, epilepsy must be defined by more than just the recurrence, or a potential for recurrence, of seizures. For some people with epilepsy, behavioral disturbances, such as interictal and postictal cognitive problems, can be part of the epileptic condition. Patients with epilepsy may suffer from stigma, exclusion, restrictions, overprotection, and isolation, which also become part of the epileptic condition. Seizures and the potential for recurrence of seizures also often have psychological consequences for the patient and for the family.

(3) At least one seizure is required to establish the presence of epilepsy; a predisposition, as determined, for example, by a family history, or by the presence of epileptiform EEG changes, is not sufficient to determine epilepsy. The definition does not include a requirement that the seizure be “unprovoked,” a feature of several prior individual definitions. Instead, the definition requires, in addition to at least one seizure, the presence of an enduring alteration in the brain.

Further questions:
1. How do we judge that an individual has "an enduring disturbance of the brain capable of giving rise to further seizures"?

Ans: to be continued....

Friday, July 13, 2012

Zinc treatment in Wilsons as paradigm shift

Paradigm shift in treatment of Wilson's disease: zinc therapy now treatment of choice
Brain Dev. 2006 Apr;28(3):141-6. Epub 2006 Feb 7. 
Hoogenraad TU.
University Department of Neurology, UMC-Utrecht, Heidelberglaan 100, 3584 CX, The Netherlands. tu.hoogenraad@planet.nl

Abstract

Zinc therapy has replaced penicillamine as first-line therapy for Wilson's disease. New guidelines reflect the paradigm shift in treatment that has occurred in recent years. In the old paradigm, Wilson's disease was seen as genetic disorder associated with the accumulation of copper in the liver and in other organs once the liver had become overloaded with copper. When left untreated, the disease was regarded as uniformly fatal. The old treatment guidelines advised, 'decoppering' with penicillamine because this chelating agent was considered effective in restoring most patients to health. Before the start of treatment, patients were warned that their symptoms could worsen during the first weeks or months of therapy, so as to prevent them from abandoning penicillamine therapy in dismay. In the new paradigm, Wilson's disease is seen as a hereditary disorder associated with copper intoxication. The essence of symptomatic Wilson's disease is poisoning by free copper in the blood, that is, by copper that is not bound to ceruloplasmin. This form of copper is toxic, whereas accumulated copper and copper that is bound to ceruloplasmin or metallothionein is not. The treatment of symptomatic Wilson's disease is no longer aimed at 'decoppering', the removal of accumulated copper, but at the normalization of the free copper concentration in blood, to reverse the copper poisoning. This can be achieved safely and effectively with zinc therapy. Zinc induces metallothionein, a highly effective detoxification protein that binds copper. Oral zinc therapy leads to storage of metallothionein-bound copper in the mucosa of the gut and to the excretion of copper via the stools. New treatment guidelines advise against the use of chelating agents as initial treatment because they may aggravate copper intoxication and cause iatrogenic deterioration.

Dorsal Midbrain (Parinaud) syndrome

http://en.wikipedia.org/wiki/Parinaud%27s_syndrome

Parinaud's Syndrome is a cluster of abnormalities of eye movement and pupil dysfunction, characterized by:
  1. Paralysis of upgaze: Downward gaze is usually preserved. This vertical palsy is supranuclear, so doll's head maneuver should elevate the eyes, but eventually all upward gaze mechanisms fail.
  2. Pseudo-Argyll Robertson pupils: Accomodation reflex present, with sluggish/ absent pupillary reflex
  3. Convergence-Retraction nystagmus: Attempts at upward gaze often produce this phenomenon. On fast up-gaze, the eyes pull in and the globes retract. The easiest way to bring out this reaction is to ask the patient to follow down-going stripes on an optokinetic drum.
  4. Eyelid retraction (Collier's sign)
  5. Conjugate down gaze in the primary position: "setting-sun sign".
It is also commonly associated with bilateral papilledema. It has less commonly been associated with spasm of accommodation on attempted upward gaze, pseudoabducens palsy (also known as thalamic esotropia) or slower movements of the abducting eye than the adducting eye during horizontal saccades, see-saw nystagmus and associated ocular motility deficits including skew deviation, oculomotor nerve palsy, trochlear nerve palsy and internuclear ophthalmoplegia.

Dysguesia causes and medicines

Common causes
Orodental infection
Upper respiratory tract infection
Sinus infection

Less common
Idiopathic dysgeusia
Mental illness (e.g. depression)
Drugs

Uncommon
Neurological
Stroke
Head trauma (e.g. fractures of the petrous temporal bone)
Cranial nerve disorders e.g. damage to the chorda tympani during
middle ear surgery
Carotid artery dissection with involvement of the chorda tympani
Facial nerve palsy
Multiple sclerosis
Borrelia burgdorferi associated - neuropathy
Gastrointestinal
Irradiation of the head and neck
Gastrointestinal reflux disease
Hepatitis and hepatic cirrhosis
Malabsorption (e.g. cystic fibrosis)
Crohn’s disease
Others
Diabetes mellitus
Niacin (vitamin B3) deficiency
Zinc deficiency
Copper deficiency
Mercury poisoning

Medications associated with altered taste
Antirheumatic agents Penicillamine, levamisole, gold, levodopa
Antithyroid agents Carbimazole, thiouracil
Anti-inflammatory agents Phenylbutazone, acetylsalicylic acid
Anti diabetic drugs Biguanides
Cytotoxic agents Doxorubicin, methotrexate, vincristine, carmustine
Diuretics and antihypertensive agents Captopril, diazoxide, ethacrynic acid
Antimicrobials Metronidazole, lincomycin, ethambutol, HIV protease inhibitors, Amphotericin
Anti-seizure agents Carbamazepine, baclofen
Others Phenindione, allopurinol, vitamin D, oral contraceptive pill