Nicholas Hirsch

Anti-N-methyl-D-aspartate receptor antibodies: a potentially treatable cause of encephalitis in the intensive care unit.

Objective: To report the occurrence of an unusual neurologic disorder requiring admission to the intensive care unit. Design: Analysis of an observational cohort study of 31 patients with encephalitis admitted over a 4-yr period. Setting: Neurologic intensive care unit in a tertiary referral center. Patients: We identified N-methyl-D-aspartate receptor antibodies in six patients (two male and four female). All seropositive patients presented with a psychiatric prodrome, before developing seizures and obtundation requiring intensive care unit admission. They exhibited limb and truncal stereotypies and orofacial dyskinesias upon weaning sedation. Two patients had ovarian tumors. Interventions: Patients were treated with sedation, antiepileptic drugs, and immunotherapy. One patient received a magnesium infusion and ketamine. Measurements and Main Results: N-methyl-D-aspartate receptor antibodies were identified in serum samples by an immunofluorescent cell-based assay. Three patients made a good but slow recovery; two were left with severe neurologic deficits; and one died after return to the referring hospital. These patients accounted for approximately 20% of all patients admitted with encephalitis to this referral center. Conclusions: N-methyl-D-aspartate receptor antibodies should be tested in patients with hyperkinetic encephalitis and neuropsychiatric prodrome admitted to the intensive care unit. The disorder is probably not rare and is potentially treatable.

Outcome of ventilatory support for acute respiratory failure in motor neurone disease

Objectives: To review the outcome of acute ventilatory support in patients presenting acutely with respiratory failure, either with an established diagnosis of motor neurone disease (MND) or with a clinical event where the diagnosis of MND has not yet been established. Methods: Outcome was reviewed in 24 patients with respiratory failure due to MND who received endotracheal intubation and intermittent positive pressure ventilation either at presentation or as a result of the unexpected development of respiratory failure. Patients presenting to local hospitals with acute respiratory insufficiency and requiring tracheal intubation, ventilatory support, and admission to an intensive therapy unit (ITU) before transfer to a regional respiratory care unit were selected. Clinical features of presentation, management, and outcome were studied. Results: 24 patients with MND were identified, all being intubated and ventilated acutely within hours of presentation. 17 patients (71%) were admitted in respiratory failure before the diagnosis of MND had been made; the remaining seven patients (29%) were already known to have MND but deteriorated rapidly such that intubation and ventilation were initiated acutely. Seven patients (29%) died on ITU (between seven and 54 days after admission). 17 patients (71%) were discharged from ITU. 16 patients (67%) received long term respiratory support and one patient required no respiratory support following tracheal extubation. The daily duration of support that was required increased gradually with time. Conclusion: When a patient with MND is ventilated acutely, with or without an established diagnosis, independence from the ventilator is rarely achieved. Almost all of these patients need long term ventilatory support and the degree of respiratory support increases with time as the disease progresses. The aim of management should be weaning the patient to the minimum support compatible with symptomatic relief and comfort. Respiratory failure should be anticipated in patients with MND when the diagnosis has been established.

Randomized controlled trial of toothbrushing to reduce ventilator-associated pneumonia pathogens and dental plaque in a critical care unit.

AIM To investigate the effect of a powered toothbrush on colonization of dental plaque by ventilator-associated pneumonia (VAP)-associated organisms and dental plaque removal. MATERIALS AND METHODS Parallel-arm, single-centre, examiner- and analyst-masked randomized controlled trial. Forty-six adults were recruited within 48 h of admission. Test intervention: powered toothbrush, control intervention: sponge toothette, both used four times per day for 2 min. Groups received 20 ml, 0.2% chlorhexidine mouthwash at each time point. RESULTS The results showed a low prevalence of respiratory pathogens throughout with no statistically significant differences between groups. A highly statistically significantly greater reduction in dental plaque was produced by the powered toothbrush compared with the control treatment; mean plaque index at day 5, powered toothbrush 0.75 [95% confidence interval (CI) 0.53, 1.00], sponge toothette 1.35 (95% CI 0.95, 1.74), p=0.006. Total bacterial viable count was also highly statistically significantly lower in the test group at day 5; Log(10) mean total bacterial counts: powered toothbrush 5.12 (95% CI 4.60, 5.63), sponge toothette 6.61 (95% CI 5.93, 7.28), p=0.002. CONCLUSIONS Powered toothbrushes are highly effective for plaque removal in intubated patients in a critical unit and should be tested for their potential to reduce VAP incidence and health complications.

Creutzfeldt-Jakob disease presenting as complex partial status epilepticus: a report of two cases

Creutzfeldt-Jakob disease is a transmissible human spongiform encephalopathy which may be familial, iatrogenic, or sporadic. The classic clinical features include a rapidly progressive dementia with the patient retaining clear consciousness until the terminal stages of the disease. We report on two patients presenting with a rapidly declining level of consciousness, in whom the clinical picture and EEG were suggestive of complex partial status epilepticus. The first patient was a 58 year old woman who was admitted to a psychiatric unit with a short history of mood disturbance, confusion, and unsteadiness. A provisional diagnosis of agitated depression was made and she was started on lofepramine. She then became unsteady on her feet and required support when walking. She had had occasional complex partial seizures for 30 years but at presentation was not taking any anticonvulsant drugs. On examination, she appeared perplexed, tearful, and agitated, and was unable to give a coherent history. She was intermittently confused and her gait was ataxic. There were no other cerebellar signs. The rest of the neurological examination was unremarkable although limited by poor cooperation. She became more withdrawn and uncommunicative with incontinence of urine. She would occasionally jump …

Respiratory insufficiency due to high anterior cervical cord infarction

OBJECTS AND METHODS Respiratory dysfunction may occur as a result of lesions in the upper cervical spinal cord disturbing the descending pathways subserving automatic and volitional ventilatory control. Four patients are described who presented with acute respiratory insufficiency caused by infarction of the anterior portion of the upper cervical cord due to presumed anterior spinal artery occlusion. RESULTS Two patients presented after respiratory arrests; they were ventilated and there was no automatic or volitional respiratory effort. Both had signs of an extensive anterior spinal cord lesion at the C2 level and this was confirmed by MRI. One patient presented with a C4 infarction and required ventilation for three months. Ventilatory recovery was characterised by the development of an automatic respiratory pattern. The fourth patient required ventilation for two months after infarction at the C3 level. On attempted weaning he had prolonged periods of hypoventilation and apnoea during inattention and sleep indicating impairment of automatic respiratory control. CONCLUSION Infarction of the spinal cord at high cervical levels may be due to fibrocartilaginous embolism and involvement of the descending respiratory pathways may occur. Extensive lesions at C1/2 cause complete interruption of descending respiratory control leading to apnoea. Partial lesions at C3/4 cause selective interruption of automatic or voluntary pathways and give rise to characteristic respiratory patterns. The prognosis depends on the level and extent of the lesion.

The management and outcome of patients with myasthenia gravis treated acutely in a neurological intensive care unit

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) over a 66 month period were reviewed. Twenty‐seven patients were admitted in myasthenic crisis, eight of whom had multiple admissions. One patient had a cholinergic crisis and a further patient an acute myocardial infarction. A specific aetiological factor precipitating myasthenic crisis was identified in 19 instances: infection (8), reduction in medication (5), menstruation (4), and steroid administration (2). Thirteen patients with crisis had had a previous thymectomy, six with thymoma. Twenty‐three out of 35 (66%) patients admitted in crisis required intubation; nine subsequently needed a tracheostomy. Twenty‐nine patients received plasma exchange and seven intravenous immunoglobulin. Four patients in myasthenic crisis died in ITU [adult respiratory distress syndrome (1), disseminated intravascular coagulation and cytomegalovirus (CMV) pneumonitis (1), cardiac failure (1) and multiple organ failure (1)]. Appropriate management of myasthenia gravis requires the easy availability of specialised neuro‐intensive care facilities.

Rituximab in the treatment of three coexistent neurological autoimmune diseases: chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis

A 76-year-old man with a pre-existing diagnosis of myasthenia gravis was admitted to an intensive care unit with pneumonia and type II respiratory failure. In addition, muscle weakness, widespread myokymia, neuropsychiatric disturbance and autonomic disturbance were present. Antivoltage gated potassium channel antibodies, antistriated muscle antibodies and antiacetylcholine receptor antibodies were positive. Nerve-conduction studies demonstrated findings consistent with patchy demyelination. Electromyography confirmed widespread myokymia, and there was evidence of diffuse encephalopathy on electroencephalography. Diagnoses of Morvan syndrome and chronic inflammatory demyelinating polyradiculopathy (CIDP) were made. Treatment with intravenous immunoglobulin, plasma exchange and high-dose steroids were ineffective, and the patient remained dependent on mechanical ventilation. The coexistence of possibly three humorally mediated autoimmune diseases led to treatment with rituximab. Rituximab treatment was followed by an improvement in muscle strength, allowing successful weaning from mechanical ventilation, diminution in myokymia and improved cognition. At follow-up, there was reversal of the neuropsychiatric manifestations and normal muscle strength. This case suggests that rituximab may be useful in the treatment of autoimmune neurological disease refractory to other immunosuppressant therapies. Specifically, it adds further evidence for the use of rituximab in CIDP. As indications for rituximab in humorally mediated disease continue to expand, international multicentre randomised controlled trials are required to prove the effectiveness of this important emerging biological agent.

Admission to neurological intensive care: who, when, and why?

The majority of neurologists work in district general or teaching hospitals with large general intensive care units (ICUs). In this setting, ICUs require an increasing input from neurologists, especially with regard to the assessment of hypoxic brain damage and the neurological complications of organ failure, critical illness, and sepsis. In contrast, dedicated neurological intensive care units (NICUs) tend to deal largely with a different population of patients. Such units are primarily concerned with the management of primary encephalopathic patients, the control of raised intracranial pressure (ICP), the management of ventilatory, autonomic, and bulbar insufficiency, and the consequences of profound neuromuscular weakness. This role encompasses the treatment of mechanical ventilatory failure, specific treatments (both medical and surgical) and general medical complications of these disorders.1 In general, NICU patients with primary neurological diseases such as myasthenia gravis, Guillain-Barre syndrome, central nervous system infections, status epilepticus, and stroke have a better outcome than those patients with secondary neurological disease seen on general ICUs. However, such patients remain dependent on ICU support for very much longer periods of time. This results in very significant psychological demands on the patients, their carers, the nurses, physicians, and other health care professionals. In this review we will consider the rationale for managing acute neurological conditions in a dedicated NICU environment. Indications for admission to NICU include: ### Box 1: …

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

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.

Late recurrent thymoma in myasthenia gravis: a case series

Between 10% and 20% of patients with myasthenia gravis (MG) have a thymoma. Complete surgical removal forms the cornerstone of treatment regimes with adjuvant radiotherapy recommended in cases of incomplete resection. Thymomas are characterised by an indolent growth with good prognosis. However, recurrence is seen in 7–30% of patients.1 Myasthenic symptoms often remain after removal of a thymoma, with over 80% of the patients requiring continued immunosuppression.2 These patients continue to attend general neurology clinics and, therefore, it is necessary that neurologists are alert to the possibility of a thymoma recurrence. We describe five patients with MG who had undergone a thymectomy but developed late recurrence of thymoma. We undertook a review of the patient records from a dedicated MG clinic at the National Hospital for Neurology and Neurosurgery and identified cases of late recurrent thymoma. ‘Late’ was defined as a recurrence appearing at least 6 years after the initial resection. This interval was chosen based on a study showing that thymoma recurrence was usually observed within 6.25 years after the initial resection.3 Over many years, all of the patients were reviewed regularly by one of …