Tag Archives: Neurology

Common confirmatory tests in Brain Death

Cerebral angiography

  • Contrast medium under high pressure in both anterior and posterior circulation injections
  • No intracerebral filling at the level of the carotid or vertebral artery entry to the skull
  • Patent external carotid circulation
  • Possible delayed filling of the superior longitudinal sinus

Electroencephalography

  • Minimum of eight scalp electrodes
  • Interelectrode dependencies should be between 100 and 10,000
  • Integrity of the entire recording system should be tested
  • There should be no electroencephalographic reactivity to intense somatosensory or audiovisual stimuli

Transcranial Doppler ultrasonography

  • Bilateral insonation
  • The probe is placed at the temporal bone above the zygomatic arch or the vertebrobasilar arteries through the suboccipital transcranial window
  • The abnormalities should include a lack of diastolic or reverberating flow, small systolic peaks in early systole, and a lack of flow found by the investigator who previously demonstrated normal velocities

Cerebral scintigraphy (technetium Tc 99m hexametazime)

  • Injection of isotope within 30 minutes of reconstitution
  • Static image of 500,000 counts at several time intervals: immediately, between 30 and 60 minutes, and at 2 hours.

Answer to CC #14

Case Challenge #14 presented a 46 year old female presenting with a persistent cough for 10 years, no significant exposures, no smoking history, no travel, and an otherwise negative ENT, allergy, GI, speech, etc. work-up. PFTs reveal obstructive pattern, but standard COPD medications do not prove to be helpful. CT reveals bilateral nodular disease and mosaicism. Biopsy of the lung reveals neuroendocrine cell hyperplasia which stain for carcinoid.

What is the best initial management strategy?

Serial CT Scans! The patient has DIPNECH (Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia)

  • Definition: Hyperplasia of bronchial neuroendocrine cells in airway epithelium with aggregates of cells (“tumorlets”) extending beyond the basement membrane
    • first described in 1992 (Aguayo et al, NEJM)
    • typically female nonsmokers, mean age 45 years
    • absence of other pulmonary processes or environmental exposures to explain symptoms
  • Presentation:
    • years of cough, +/- wheeze and dyspnea
    • PFTs: irreversible airflow obstruction & a third of patients had restriction
    • CT: multiple nodules and air-trapping due to bronchiolitis. Moasaicism.
  • Management: “…longterm follow-up and treatment remains incomplete…” (Am J Resp Crit Care 2011)
    • COPD management: BA +/- inhaled or systemic steroids for symptomatic relief
    • Serial CTs to watch for development of carcinoid tumors
      • “Given its only minor risk of invasive metastatic spread, serial imaging for timely detection of progressing lesions and optimizing of concomitant obstructive pulmonary disease are the preferred treatment approaches.” (Dtsch Med Wochenschr. 2014 Jun;139(23):1245-8. doi: 10.1055/s-0034-1370073. Epub 2014 May 27.)
    • There is some evidence that somatostatin analogues are helpful, but long-term safety and efficacy data are lacking

Case challenge #14 (aka the Parkland Files!) will be posted next week!    

Answer to CC #13

Case challenge # 13 presented a 20-year-old white male with fever, conjunctival injection, cervical lymphadenopathy, cracked/red lips, a macular rash, swelling in his hands, a history of tonsillar abscess, and elevated inflammatory markers. Work-up for infectious disease and auto-immune disease are negative.

What is the most likely diagnosis?Screen Shot 2015-04-24 at 7.04.50 PM

The correct answer is Kawasaki Disease!
  • Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute necrotising vasculitis of the medium- and small-sized vessels. It was first described by Tomisaki Kawasaki in 1967. It occurs most often in babies and children, aged 6 months to 5 years and the male-to-female ratio ranges from 1.5–1.8 to 1. KD is most prevalent in Japan, while Korea holds the second place as to the number of patients. Its incidence in Japanese and Korean children living in the USA and following a Western lifestyle is higher than in Caucasian children. Since the disease is not common in adults, it is very often misdiagnosed. As of earlier this year, approximately 100 cases in the world population. 
  • Diagnostic Criteria: Fever persisting at least 5 days and the presence of at least 4 of the following 5 principal features:

    1. Changes in extremities: Acute: Erythema and edema of hands and feet Convalescent: Membranous desquamation of fingertips

    2. Polymorphous exanthema

    3. Bilateral, painless bulbar conjunctival injection without exudate

    4. Changes in lips and oral cavity: Erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae

    5. Cervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral

    *Patients with fever and fewer than 4 principal symptoms can be diagnosed as having Kawasaki disease when coronary artery disease is detected by 2-dimensional echocardiography or coronary angiography. Other diagnoses should be excluded. The physician should be aware that some children with illness not fulfilling these criteria have developed coronary artery aneurysms.

Case challenge #14 (aka the Parkland Files!) will be posted next week!

 

 

Answer to CC #12

Case challenge # 12 presented a 27 year old black female with descending numbness, paresthesias, and blurry vision. The exam confirms her complaints, and lumbar puncture reveals a lymphocytic pleocytosis. The MRI findings, seen below, reveals inflammation of the right optic nerve, but no brain parenchymal findings.

NMO MRI

What is the most likely diagnosis?

 
The correct answer is Devic’s Disease (Neuromyelitis Optica)!
  • Optic neuritis and cervical myelopathy
  • Can be difficult to distinguish from MS, but is a distinct entity
  • CSF may have neutrophilic pleocytosis, but negative for oligoclonal bands in up to 85% of cases
  • NMO-IgG binds to Aquaporin-4 channel in the astrocyte foot process at the blood-brain barrier. Testing for this antibody is both sensitive and specific.
  • No controlled trials evaluating therapy – usually IV steroids and PLEX, followed by systemic immuno-suppresion to prevent recurrent episodes.

Case challenge #13 (aka the Parkland Files!) will be posted next week!

 

 

Neurosyphilis

Background

Neurosyphilis is a slow progressive, destructive infection of the brain and spinal cord caused by the spirochete T. pallidum. Its incidence has declined markedly since the introduction of penicillin therapy. It can occur at any stage of syphilis, although symptomatic early neurosyphilis is a rare manifestation.

Clinical Manifestations

Early diagnosis of neurosyphilis and appropriate antibiotic treatment make notable clinical improvement. However, the clinical diagnosis of neurosyphilis is often difficult because most patients are asymptomatic or present with non-specific symptoms such as memory disturbance or seizures.

Presentations range from asymptomatic neurosyphilis to meningitis and general paresis. Acute syphilitic meningitis (6% of syphilis patients) is typically the earliest manifestation of neurosyphilis. It is often associated with cranial nerve palsies, fever, headache, meningismus, and may even have signs of cortical involvement. Meningovascular syphilis (up to 12% of patients) can present at endarteritis, causing infarction clinically similar to a stroke. Tabes dorsalis, the disease of the posterior columns of spinal cord occurs more than 20 years after initial infection. Now exceedingly rare, it often coexists with general paresis. This typically manifests as an abnormal gait, paresthesias, lightning pains of extremities, loss of proprioception on exam, and a positive Romberg. The famous Argyll-Robertson pupils may be seen with Tabes Dorsalis or with general paresis. Notably, the psychiatric manifestations of neurosyphilis have garnered significant interest, historically. Syphilitic infection of the meninges and cortex causes personality changes, paranoia, emotional lability, eventually progressing to memory loss and dementia.

Diagnosis

CSF examination is recommended in all patients with untreated syphilis of unknown duration or of duration greater than one year. The diagnosis of neurosyphilis is based on a CSF WBC count of 20 cells/μL or greater, and/or a reactive CSF Venereal Disease Research Laboratory (VDRL) test, and/or a positive CSF intra-thecal T. pallidum antibody index. Other CSF abnormalities include elevated protein levels and pleocytosis, which are found in up to 70 percent of patients. In addition, the CSF VDRL result is reactive. Some experts advise lumbar puncture in patients with secondary and early latent syphilis. This is because standard penicillin G benzathine therapy for early syphilis does not achieve treponemicidal levels in the CSF.

Management

The recommended regimen is 14 days of aqueous benzylpenicillin IV, administered daily in doses of 2–4 million IU, every 4 hours. If IV therapy is unavailable or not well suited to the individual situation, an alternative regimen is to use procaine benzylpenicillin, 1.2 million IU by IM injection, once daily, and probenecid, 500 mg orally, 4 times daily, both for 10–14 days. Outpatient compliance must be certain (i.e. consider OPAT clinic!).

For penicillin-allergic, non-pregnant patients, we can use doxycycline 200 mg PO twice daily for 30 days, OR tetracycline 500 mg PO 4x daily for 30 days. These alternatives to penicillin have not been evaluated in systematic studies.

Journal of Medical Case Reports 2012, 6:389.

Hospital Physician 2009, 45(1).

Int J STD AIDS 1993, 4(2):70-82.

Arch Neurol 1985 Jun;42(6):606-13.

Guidelines for the management of sexually transmitted infections. World Health Organization. 2001 : Geneva, Switzerland. ISBN 92 4 154626 3.

Neuro-Behcet Disease

General Information

  • Excluding headaches, neurological complications of Behçet syndrome (neuro-Behçet syndrome) occur in less than 12% of cases, often a few years after the onset of the other systemic features.

Clinical Manifestations and Diagnosis

  • In parenchymal disease, meningoencephalitis occurs, with a mixed inflammatory cell infiltrate leading to necrosis and apoptotic neuronal loss. Inflammatory infiltration, rather than fibrinoid necrosis, is seen around small vessels.
    • The brainstem and mid-brain are the most commonly affected areas, but spinal cord lesions and cerebral involvement may also occur and, occasionally, neuro-Behçet syndrome presents as a pseudotumour cerebri.
    • Brainstem involvement usually presents subacutely, with headache, cranial neuropathies or cerebellar or corticospinal tract dysfunction.
    • Sensorineural hearing loss can occur, resulting in sudden deafness, balance disturbances and dizziness.
    • The characteristic MRI lesion in parenchymal neuro-Behçet syndrome is a unilateral upper brainstem lesion extending into the thalamus and basal ganglia.
    • Analysis of cerebrospinal fluid shows a neutrophilic (in early disease) or lymphocytic (in late disease) pleocytosis, but usually no oligoclonal bands.
  • Neurovascular disease accounts for approximately 20% of cases of neuro-Behçet syndrome and symptoms include dural sinus thrombosis, intracranial aneurysm and extracranial aneurysm and/or dissection.
    • The clinical findings are usually limited to those of intracranial hypertension (that is, headache, vomiting, altered levels of consciousness and papilloedema).
    • Intracranial hypertension may be present without MRI abnormalities and should be managed in the same way as idiopathic benign intracranial hypertension.
    • Aneurysms of the cerebral, vertebral and carotid arteries can also occur.

Management

  • Headaches are often under-treated. An effort should be made to classify the type of headache and, in the case of migraine, agents such as pizotifen and β­blockers should be offered.
  • Parenchymal disease:
    • Initial Management: treated with high-dose steroids in the first instance, along with initiation of a DMARD, usually azathioprine.
      • Methotrexate, mycophenolate, cyclophosphamide, tacrolimus and IFN-­α are probably effective, although evidence is lacking.
      • Cyclosporin is potentially neurotoxic and should not be used for patients with a history of CNS disease.
    • The alternative therapeutic option for severe and aggressive disease is the early use of a biologic agent (i.e. anti-TNF therapy, like infliximab)
  • Neurovascular disease:
    • Cerebral vascular thrombosis and aneurysms also require aggressive immunosuppression.
    • Anti-coagulation for venous thrombosis needs to be assessed on a case-by-case basis.

Ambrose, N. L. & Haskard, D. O. Nat. Rev. Rheumatol. 9, 79–89 (2013); published online 25 September 2012; doi:10.1038/nrrheum.2012.156

Myxedema Madness

Introduction

The term “Hashimoto encephalopathy” (HE) was used perhaps for the first time in 1991 by Shaw (1), who collected five cases with similar symptoms such as seizures, disorientation, frequent episodes of alternating hemiparesis, high protein levels in the cerebrospinal fluid and electrocardiographic abnormalities. However, these patients also had hypothyroidism and positive thyroid antibodies. However, in 1966, a case was described of a 63-year-old man who had seizures, disorientation, frequent episodes of alternating hemiparesis, high protein levels in the cerebrospinal fluid, electrocardiographic abnormalities and biopsy-confirmed Hashimoto thyroiditis (2) Because several cases were later published that showed a similar outcome but with entirely different clinical presentations, the question has been raised whether HE is a true syndrome. The same authors concluded that several patients presented with various signs of encephalopathy and high thyroid antibody levels together with the responsiveness to glucocorticoid therapy and that such convergence seems unlikely to result from chance (3). There also appears to be no evidence of any specific pathogenic role for thyroid antibodies in the origin of such encephalopathy, and several authors hypothesized that these antibodies are only markers of a possibly unrelated autoimmune disease affecting the brain. The term HE is now commonly used for the few hundred patients published so far, whereas some other terms such as “myxedema madness” (4), “encephalopathy associated to autoimmune thyroid disease” (5) or “steroid-responsive encephalopathy with antibodies to thyroperoxidase” (SREAT) (6) have been mostly abandoned.

Clinical presentation

HE is a relatively rare condition with a broad range of clinical presentation. Thus, there is a high risk that patients with this serious disease will be misdiagnosed and thus even mistreated, sometimes for a considerably long time. Because the finding of TPOab in blood is one of the most frequent signs accompanying HE, it is generally recommended as a powerful diagnostic tool in all cases of unexplained fluctuating encephalopathy. The most frequently observed signs include epilepsy-like seizures resistant to anticonvulsive treatment, confusion, headaches, hallucinations, stroke-like episodes, coma, impairment of cognitive function, behavioral and mood disturbance, focal neurological deficits, disturbance of consciousness, ataxia, and presenile dementia.
Although the majority of described cases showed neural symptoms for months before the acute onset, in some cases a dramatic acute onset appeared. A review of 30 patients revealed two types of clinical presentation, e.g., that with acute or insidious onset (21). In general, this view seems to be supported by an overview of several patients as summarized below. However, a third type of onset and clinical course of a variety of neurologic complications was recently defined as “relapsing-remitting manner including cognitive deterioration and psychiatric illness” (8).
HE appears in all age groups including children (22), and as much as approximately 70 to 80 percent of the patients are women and girls. It was repeatedly underlined that, especially in children, several cases of such encephalopathy remained unrecognized for a considerable time (8, 23, 24). However, in several cases, a clear thyroid disorder, mostly presenting as hypofunction, could provide useful streamlining diagnostic guidance in patients with various neuropsychiatric signs. Such signs usually continue after the thyroid treatment or even show a worsening that is generally considered to be one of the most important signs of HE, as the specific neuropsychiatric problems usually accompanying each thyroid disorder disappear after treatment with thyroxine.

Diagnosis

Some useful reports have appeared regarding the frequency of individual symptoms and/or laboratory findings in patients with HE. Chong et al. (3) summarized 105 cases and concluded that in most cases, the diagnosis was based on the disturbed consciousness, negative finding of bacterial or viral infection in the cerebrospinal fluid, and high level of thyroid antibodies, with latter found in 100% of the cases, although the antibody level usually did not appear to be correlated with the severity of the illness. Moreover, a high protein level in the cerebrospinal fluid appeared in 78% of cases, abnormal electroencephalography in 98% and various mostly nonspecific abnormalities on magnetic resonance imaging in approximately 50%. Magnetic resonance revealed ischemic areas, multiple tumors, granulomas or various degenerative processes in 60% of the cases, and SPECT examinations showed decreased perfusion in the cortical areas or basal ganglia (25). From 1995 to 2003, 20 patients with Hashimoto encephalopathy were examined (26) and tremor was found in 16, transient aphasia in 16, myoclonus in 13, walking impairments in 13, seizures in 12 and sleeping disorders in 11 of them.

=== CSF Analysis
Cerebrospinal fluid analysis, electroencephalography, and neuroimaging studies do not show consistent findings to support the diagnosis. Physicians’ awareness of this complication is of great importance because most patients respond dramatically to corticosteroid therapy. Moreover, early recognition might also prevent a costly diagnostic work-up in patients with unexplained encephalopathy. In one patient, a follow-up for the IgG level in the CSF was found to be useful; after the IgG was found to be increased, the treatment was repeated with a partial clinical improvement and decline in the CSF level of IgG. Following high-dose steroid treatment, the patients’ clinical condition stabilized and a CSF analysis showed even further IgG decline (27). Thus far, approximately 150 cases have been published, although this disease probably remains under-diagnosed because it is not yet generally known and there were also presumably several additional cases that simply were not published at all. As clearly follows from the literature, an unusually wide variety of symptoms at presentation effectively obscures the basic pathogenetic process of HE. Because thyroid antibodies recently became considered as a useful marker for HE, it is recommended to check for their elevation not only in the blood but also in the CSF, particularly in cases presenting the triad of encephalopathy with EEG slowing and increased protein level in the CSF as well as in all unexplained cases with a variety of nonspecific neuropsychiatric symptoms, generalized or partial seizures, hallucinations, or status epilepticus.

=== MRI
The MRI manifestations of HE can vary from normal appearance, ischemic lesions, demyelination, and vasogenic edema to atrophy. The diverse MRI features of HE reported in the literature make it difficult to understand the pathological process and monitor the prognosis. To investigate the dynamic changes of MRI manifestations in HE, two cases of HE were retrospectively analyzed with a series of longitudinal MRI data. Although similar acute ischemic manifestations were observed at the onset of HE in both cases, at follow-up, we observed different evolutions of HE on MRI between the two cases, which might partially account for the diversity of MRI findings (for example, a certain stage of HE). The clinical and MRI findings at follow-up also indicated that early treatment contributed to the recovery of the lesions (28).

Treatment

Once a firm HE diagnosis is made, corticosteroid treatment usually provides a dramatic recovery, but several adverse outcomes, relapses and temporary or permanent spontaneous remissions have also been reported. At the same time, the high effectiveness of corticoid treatment in nearly all HE patients strongly supports an common autoimmune origin. Even in the absence of diagnostic serological findings, clinical improvement with corticosteroids may be provide the only evidence of autoimmune encephalopathy (29). However, it is always necessary to consider the possible adverse effects of corticosteroid therapy (30). Additionally, a case of HE was described that improved only after intravenous immunoglobulin treatment (31).

 

International Journal of Endocrinology and Metabolism. 2012 December; 10(2): 506-514. , DOI: 10.5812/ijem.4174

#clinicalpearls

Common Pharmacologic Precipitants of Myasthenic Crisis

Patients with myasthenia gravis  may be seen in the emergency department for symptoms that are  not related to their MG, such as an upper respiratory tract infection or chest pain.

Physicians should be careful in prescribing new medications to patients with MG, as that can precipitate a myasthenic crisis (and therefore cause significant morbidity and mortality). Below is a list of medications that are commonly implicated; an extensive list can be found at www.myasthenia.org/docs/MGFA_medicationsandmg.pdf)

  • Iodinated IV contrast
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides
  • IV magnesium replacement
  • Beta blockers (metoprolol and labetalol)

Normal Pressure Hydrocephalus

General Information

Normal pressure hydrocephalus (NPH) is a syndrome characterized by gait impairment, cognitive decline, and urinary incontinence, and is associated with ventriculomegaly in the absence of elevated cerebrospinal fluid (CSF) pressure.

  • Idiopathic NPH: without known precipitant
  • Secondary NPH: occurs due to other disease processes, including subarachnoid hemorrhage, traumatic brain injury, cerebral infarction and meningitis

Clinical Presentation

  • Triad of gait disturbance, dementia and urinary incontinence
    • The entire triad need not be present
    • Symptoms typically develop insidiously
    • Generally occurs between the sixth and eighth decades of life
  • Gait disturbances: typically the first signs of INPH, and have been variously described as apraxic, bradykinetic, glue-footed, magnetic, parkinsonian and shuffling; often present with a history of falls; no significant motor weakness.
  • Cognitive deficits: typically of the subcortical type, characterized by inattention, psychomotor retardation and difficulty with executive function.
  • Urinary Incontinence: in the early stages of INPH, urinary frequency and urgency are present. With disease progression, urinary and even fecal incontinence can be observed. Urodynamic testing demonstrates bladder hyperactivity

Differential Diagnosis

  • Neurodegenerative diseases, vascular etiologies and urological disorders: peripheral neuropathy, cervical or lumbar stenosis, arthritis, vestibular diseases and Parkinson’s disease.
  • Dementia: Alzheimer’s dementia, diffuse Lewy body disease and vascular dementia – the absence of apraxia, agnosia and aphasia can help differentiate INPH from cortical dementias.

Diagnosis: based on history, physical exam, neuroimaging, and exclusion of other causes.

  • Imaging:
    • CT or MRI to assess ventricular size
      • Ventricular enlargement is necessary to establish the diagnosis of INPH for patients with appropriate symptoms
      • A frontal horn ratio (Evans’ index), defined as the maximal frontal horn ventricular width divided by the transverse inner diameter of the skull, signifies ventriculomegaly if it is 0.3 or greater.
    • Other radiographic findings associated with INPH include the following:
      • Periventricular hyperintensities, which are often associated with subcortical microvascular ischemia
      • Increased CSF flow velocity in the aqueduct
      • Thinning and elevation of the corpus callosum on sagittal images
      • No visible evidence of obstruction to CSF flow.
    • Lumbar Puncture: large-volume LP, involves the withdrawal of 40–50 ml of CSF
      • Symptomatic improvement after CSF removal increases the likelihood of a favorable response to shunt placement (positive predictive value 73–100%)
      • Low sensitivity (26–61%), however, and a negative test cannot be used to exclude a diagnosis of INPH

Treatment:

Accomplished through surgical diversion of CSF. This is accomplished by implanting a shunt to drain CSF from either the intracranial ventricular system or the lumbar subarachnoid space to a distal site, such as the peritoneal or pleural cavity or the venous system, where the CSF can be reabsorbed. The most common shunts utilized today are ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts.

Nature Clinical Practice Neurology (2005) 2, 375-381; doi:10.1038/ncpneuro0237

Image courtesy of Radiopaedia.org