Changes in the severity and subtype of Guillain-Barré syndrome admitted to a specialist Neuromedical ICU over a 25 year period.

We report a retrospective review of 110 patients with acute Guillain-Barré syndrome (GBS) admitted to a specialised intensive care unit (ICU) in a tertiary referral centre over a 25 year period, the start of which coincided with the widespread introduction of plasma exchange (PE) and intravenous immunoglobulin (IVIG). The results were analysed by comparing 52 patients admitted in the first decade (1991-2000; Group 1) with 58 patients admitted between 2001-2014 (Group 2). Patients in both groups were comparable with respect to age and sex, and had a similar incidence and range of ICU complications. They received a comparable range of immunomodulatory treatments including IVIG and PE. However, the delay from presentation to referral to the tertiary ICU was longer in patients in Group 2. They also required mechanical ventilation for a longer duration, and had longer ICU and hospital stays. In Group 2, there was a higher incidence of axonal neuropathy (51%, compared to 24% in Group 1). Despite the longer delay to referral, the prevalence of axonal neuropathy and the duration of ventilation, overall mortality showed a downward trend (Group 1: 13.5%; Group 2: 5.2%). There was no late mortality in either group after step-down to neuro-rehabilitation or following discharge home or to the referring hospital. The rehabilitation outcomes were similar. This data show a shift in the pattern of referral to a tertiary referral ICU between the first and second decades following the wider availability of IVIG and PE for the treatment of GBS. The possible causes and implications of these findings are discussed.

Myasthenia gravis--treatment of acute severe exacerbations in the intensive care unit results in a favourable long-term prognosis.

BACKGROUND AND PURPOSE: Acute severe exacerbations of myasthenia gravis (MG) are common in both early and late onset MG. We wished to examine the current management in the intensive care unit (ICU) of severe exacerbations of MG and to study the long-term prognosis of MG following discharge from the ICU. METHODS: We retrospectively reviewed the medical records of all patients admitted to a specialist neuro-ICU with acute exacerbations of MG over a 12-year period. RESULTS: We identified 38 patients. Over 60% were over the age of 50 years, and MG was newly diagnosed in over 40%. Intubation was required in 63%, and over 90% of patients were treated with prednisolone and/or intravenous immunoglobulin. Four patients died in hospital. The remainder of patients were followed up for a mean of 4 years, and the majority were either asymptomatic or had mild symptoms of MG at clinical review. CONCLUSIONS: Despite the significant morbidity and mortality associated with severe exacerbations of MG, specialized neurointensive care can result in a good long-term prognosis in both early- and late-onset MG.

Thymectomy: role in the treatment of myasthenia gravis.

Thymectomy is a frequently used treatment for myasthenia gravis (MG) and is virtually always indicated in MG patients who have a thymoma. However, the evidence for thymectomy in non-thymomatous MG remains less certain-no randomised controlled trials have been published to date, although one is currently underway. We reviewed the management and clinical outcome of patients with MG who underwent thymectomy over a 12 year period. Eighty-nine patients who underwent transsternal thymectomy were identified. A thymoma was identified on histology in 24 %, whereas 48, 9 and 19 % had hyperplastic, atrophic and normal thymic histology, respectively. One patient developed post operative myasthenic crisis but generally the procedure was well tolerated. Outcome was favourable for the majority of patients, with 34 % achieving complete stable remission (CSR) and an additional 33 % achieving pharmacological remission. Moreover, steroid requirements fell progressively during follow-up. Patients with a hyperplastic gland had a significantly greater chance of achieving CSR compared to other histological subtypes and the incidence of CSR increased with a longer duration of follow-up. Thymectomy for MG is generally safe and well tolerated and is associated with a sustained improvement of symptoms in the majority of patients.

Clinical evaluation of stethoscope-guided inflation of tracheal tube cuffs.

Tracheal tube cuffs are commonly inflated to pressures exceeding the recommended upper limit of 30 cmH(2)O. We evaluated whether a stethoscope-guided method of cuff inflation results in pressures within the recommended range. Patients were randomly assigned to receive one of two methods of cuff inflation. In the standard 'just seal' group, air was introduced into the tracheal cuff until the audible leak at the mouth disappeared. In the stethoscope-guided group, air was introduced into the cuff until a change from harsh to soft breath sounds occurred, whilst listening with a stethoscope bell placed over the thyroid cartilage. Twenty-five patients were recruited to each group. The median (IQR [range]) cuff pressure in the 'just seal' group was 34 (28-40 [18-49]) cmH(2)O, and in the stethoscope-guided group was 20 (20-26 [16-28]) cmH(2)O, p < 0.0001. The stethoscope-guided method of tracheal tube cuff inflation is a novel, simple technique that reliably results in acceptable tracheal cuff pressures.

CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain-Barré syndrome.

Early predictors of prognosis in Guillain-Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision-making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F-score). Poor outcome was defined as the inability to walk independently (F-score > or = 3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F-score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels.

Neuromuscular junction in health and disease.

A number of illnesses and other factors can affect the function of the neuromuscular junction (NMJ). These may have an affect at pre- or post-junctional sites. This review outlines the anatomy and the physiology of the NMJ. It also describes the mechanisms and physiological basis of many of the disorders of the NMJ. Finally, the importance of these disorders in anaesthetic practice is discussed.

CSF neurofilament levels: a potential prognostic marker in Guillain-Barré syndrome.

Long-term morbidity from Guillain-Barré syndrome (GBS) is caused by axonal damage. This prospective study demonstrated that neurofilaments (NfHs), a biomarker for axonal damage, were of prognostic value in GBS. CSF NfH levels correlated with the F score and Medical Research Council summed score and were higher in patients with neurophysiologic evidence of axonal degeneration compared to those without. Pathologically high CSF NfH levels (>0.73 ng/mL) predicted worse motor and functional outcome.

Management of subarachnoid haemorrhage in a non-neurosurgical centre.

Subarachnoid haemorrhage is a common neurological emergency, which carries a high morbidity and mortality. It is usually caused by rupture of an intracerebral aneurysm or, less commonly, an arteriovenous malformation. Although most patients present to a non-neurosurgical hospital, they often require urgent neurosurgical or neuroradiological intervention. Whilst awaiting transfer to a neurological centre, active management of the patient must be instituted. This should include confirmation of the diagnosis with CT imaging, lumbar puncture or both, and recognition of the complications of subarachnoid haemorrhage, which include hydrocephalus, further haemorrhage and cerebral vasospasm. Medical management is directed towards maintaining adequate cerebral perfusion pressure whilst avoiding large increases in arterial blood pressure. Nimodipine therapy must be started early in an attempt to prevent cerebral vasospasm. The treatment options available at the neurological centre include surgical treatment or endovascular obliteration of the aneurysm or arteriovenous malformation.

Brain stem encephalitis caused by primary herpes simplex 2 infection in a young woman.

A 27 year old woman developed a vesicular genital rash and cerebellar dysfunction with progressive neurological deterioration suggesting brain stem encephalitis. Respiratory support was required. Magnetic resonance imaging (MRI) of the brain on day 7 showed signal hyperintensity in the central medulla and ventral pons, typical of acute inflammation. The course was severe and relapse occurred. MRI on day 33 showed a haemorrhagic area in the medulla. Treatment with aciclovir/valaciclovir eventually led to gradual recovery. Herpes simplex virus 2 (HSV-2) DNA was detected in CSF on days 11 and 14. HSV-2 was also detected in vesicle fluid from the genital rash. Serum was initially negative for HSV-1 and HSV-2 antibodies, but convalescent samples showed seroconversion to HSV-2, indicating primary infection. Intrathecal synthesis of oligoclonal IgG bands specific for HSV was identified in the CSF. It is important to differentiate HSV-2 from HSV-1, and primary from initial or reactivated infection, so that prolonged aciclovir treatment followed by prophylaxis is instituted to prevent the high likelihood of symptomatic relapse in primary HSV-2 infection.

Neurofibromatosis: clinical presentations and anaesthetic implications.

The neurofibromatoses are autosomal dominant diseases that have widespread effects on ectodermal and mesodermal tissue. The commonest member of the group is neurofibromatosis type 1 (NF1) which varies in severity but which can affect all physiological systems. Neurofibromas are the characteristic lesions of the condition and not only occur in the neuraxis but may also be found in the oropharnyx and larynx; these may produce difficulties with laryngoscopy and tracheal intubation. Pulmonary pathology includes pulmonary fibrosis and cystic lung disease. The cardiovascular manifestations of NF1 include hypertension, which may be associated with phaeochromocytoma or renal artery stenosis. Neurofibromas may also affect the gastrointestinal tract and carcinoid tumours may be found in the duodenum. This review documents the aetiology and clinical manifestations of the neurofibromatoses and discusses their relevance to the anaesthetist.

Status epilepticus.

Status epilepticus is a medical emergency that requires rapid and vigorous treatment to prevent neuronal damage and systemic complications. Failure to diagnose and treat status epilepticus accurately and effectively results in significant morbidity and mortality. Cerebral metabolic decompensation occurs after approximately 30 min of uncontrolled convulsive activity, and the window for treatment is therefore limited. Therapy should proceed simultaneously on four fronts: termination of seizures; prevention of seizure recurrence once status is controlled; management of precipitating causes of status epilepticus; management of the complications. This article reviews current opinions about the classification, aetiology and pathophysiology of adult generalised convulsive status epilepticus and details practical management strategies for treatment of this life-threatening condition.

Status dystonicus: the syndrome and its management.

Patients with dystonic syndromes sometimes develop increasingly frequent and relentless episodes of devastating generalized dystonia which we call status dystonicus. Twelve cases of status dystonicus, of various underlying aetiologies, are presented. Possible precipitating factors were identified in only five cases: intercurrent infection (one); discontinuation of lithium (one) and tetrabenazine (one); and the introduction of clonazepam (two). Nine patients required mechanical ventilation and three others were sedated with intravenous chlormethiazole. Drug therapy used included benzhexol, tetrabenazine, pimozide, baclofen, chlorpromazine, haloperidol, carbamazepine and acetozolamide. Two patients underwent thalamotomies, one of whom improved. Two patients died, five returned to their pre-status dystonicus condition, two eventually made a full recovery and three were worse. Patients with status dystonicus should be managed on an intensive care unit as they may develop bulbar and respiratory complications which may require ventilation. Metabolic problems encountered can include rhabdomyolysis with acute renal failure. Drug therapy with benzhexol, tetrabenazine and pimozide or haloperidol may be beneficial in some cases.