Benjamin R. Wakerley

Guillain–Barré and Miller Fisher syndromes—new diagnostic classification

Guillain–Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations. Although the typical clinical features of GBS and MFS are well recognized, current classification systems do not comprehensively describe the full spectrum of either syndrome. In this Perspectives article, GBS and MFS are classified on the basis of current understanding of the common pathophysiological profiles of each disease phenotype. GBS is subclassified into classic and localized forms (for example, pharyngeal–cervical–brachial weakness and bifacial weakness with paraesthesias), and MFS is divided into incomplete (for example, acute ophthalmoparesis, acute ataxic neuropathy) and CNS subtypes (Bickerstaff brainstem encephalitis). Diagnostic criteria based on clinical characteristics are suggested for each condition. We believe this approach to be more inclusive than existing systems, and argue that it could facilitate early clinical diagnosis and initiation of appropriate immunotherapy.

Pharyngeal-cervical-brachial variant of Guillain–Barré syndrome

The pharyngeal-cervical-brachial (PCB) variant of Guillain–Barré syndrome is defined by rapidly progressive oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs. Serial nerve conduction studies suggest that PCB represents a localised subtype of Guillain–Barré syndrome characterised by axonal rather than demyelinating neuropathy. Many neurologists are unfamiliar with PCB, which is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism. The presence of additional ophthalmoplegia and ataxia indicates overlap with Fisher syndrome. Half of patients with PCB carry IgG anti-GT1a antibodies which often cross-react with GQ1b, whereas most patients with Fisher syndrome carry IgG anti-GQ1b antibodies which always cross-react with GT1a. Significant overlap between the clinical and serological profiles of these patients supports the view that PCB and Fisher syndrome form a continuous spectrum. In this review, we highlight the clinical features of PCB and outline new diagnostic criteria.

Infectious and noninfectious triggers in Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is the commonest cause of acquired flaccid paralysis in the world and regarded by many as the prototype for postinfectious autoimmunity. Here the authors consider both infectious and noninfectious triggers of GBS and determine where possible what immunological mechanisms may account for this association. In approximately two-thirds of cases, an infectious trigger is reported in the weeks that lead up to disease onset, indicating that the host’s response to infection must play an important role in disease pathogenesis. The most frequently identified bacteria, Campylobacter jejuni, through a process known as molecular mimicry, has been shown to induce cross-reactive anti-ganglioside antibodies, which can lead to the development of axonal-type GBS in some patients. Whether this paradigm can be extended to other infectious organisms or vaccines remains an important area of research and has public health implications. GBS has also been reported rarely in patients with underlying systemic diseases and immunocompromised states and although the exact mechanism is yet to be established, increased susceptibility to known infectious triggers should be considered most likely.

Idiopathic intracranial hypertension

Background Idiopathic intracranial hypertension or pseudotumour cerebri is primarily a disorder of young obese women characterised by symptoms and signs associated with raised intracranial pressure in the absence of a space-occupying lesion or other identifiable cause. Summary The overall incidence of idiopathic intracranial hypertension is approximately two per 100,000, but is considerably higher among obese individuals and, given the global obesity epidemic, is likely to rise further. The pathophysiology of this condition is poorly understood, but most theories focus on the presence of intracranial venous hypertension and/or increased cerebrospinal fluid outflow resistance and how this relates to obesity. A lack of randomised clinical trials has resulted in unsatisfactory treatment guidelines and although weight loss is important, especially when used in conjunction with drugs that reduce cerebrospinal fluid production, resistant cases remain difficult to manage and patients invariably undergo neurosurgical shunting procedures. The use of transverse cerebral sinus stenting remains contentious and long-term benefits are yet to be determined. Conclusion An understanding of the clinical features, diagnostic work-up and therapeutic options available for patients with idiopathic intracranial hypertension is important both for neurologists and ophthalmologists as visual loss maybe permanent if untreated.

Mimics and chameleons in Guillain–Barré and Miller Fisher syndromes

Guillain–Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS) have several subtypes, together forming a continuous spectrum of discrete and overlapping syndromes. Such is the heterogeneity within this spectrum that many physicians may be surprised to learn that these disorders are related pathophysiologically, and therefore share certain clinical features. These include history of antecedent infection, monophasic disease course and symmetrical cranial or limb weakness. The presence of cerebrospinal fluid albuminocytological dissociation (raised protein, normal cell count), antiganglioside antibodies and neurophysiological evidence of axonal or demyelinating neuropathy also support a diagnosis in many cases, but should not be relied upon. Mimics of GBS and MFS can broadly be divided into those presenting with symmetrical limb weakness and those presenting with brainstem signs. MFS and the pharyngeal-cervical-brachial variant of GBS are frequently mistaken for brainstem stroke, botulism or myasthenia gravis, whereas Bickerstaffs brainstem encephalitis is often diagnosed as Wernickes encephalopathy. Chameleons or atypical presentations of GBS-related disorders include: paraparetic GBS, bifacial weakness with paraesthesias, acute ataxic neuropathy, acute ophthalmoparesis, acute ptosis and acute mydriasis. Many neurologists may also not be aware that deep tendon reflexes remain present or may even appear brisk in up to 10% of patients with GBS. Correct diagnosis of GBS-related disorders helps to avoid unnecessary investigations and allows early immunotherapy if appropriate.

Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129

In this case study, variant Creutzfeldt–Jakob disease (CJD) is shown to occur in a young man with heterozygosity, rather than homozygosity, at codon 129 of the prion protein gene (PRNP).

Usefulness of Transcranial Doppler-Derived Cerebral Hemodynamic Parameters in the Noninvasive Assessment of Intracranial Pressure

Transcranial Doppler (TCD) ultrasonography is a noninvasive bedside tool that can evaluate cerebral blood flow hemodynamics in major intracranial arteries. TCD‐derived pulsatility index (PI) is believed to be influenced by intracranial pressure (ICP).

Assessment of Intracranial Collaterals on CT Angiography in Anterior Circulation Acute Ischemic Stroke

Different methods of assessing collateral circulation based on CTA were compared in 200 patients with stroke. Only the Miteff scoring system was reliable for predicting favorable outcome in these patients but poor outcomes were predictedby othermethods, too (Maas, Tan, and ASPECTS). BACKGROUND AND PURPOSE: Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010–2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0–1 and 5–6 points, respectively. RESULTS: Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079–1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560–20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203–5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113–6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075–6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156–6.237; P = .022) were independent predictors of extremely poor outcomes. CONCLUSIONS: Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.

Early and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke

BACKGROUND Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months. METHODS Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1. RESULTS Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P<.001) were independent predictors of favorable outcomes at 3 months. CONCLUSIONS Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

Red ear syndrome: a review of all published cases (1996-2010).

Background Red ear syndrome is characterised by episodic unilateral erythema of the ear associated with pain and burning sensation. Patients and methods We describe the case of a young woman with daily, frequent, recurrent episodes of red ear syndrome in the absence of any structural lesions, primary headache disorder or obvious triggers. We review all previously described cases and discuss postulated mechanisms for this syndrome. Conclusions The exact cause of this rare headache disorder remains unknown and treatment options vary considerably.