Search

Background Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies. Case presentation and literature review A 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed. Conclusion Our case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.

Pituitary apoplexy is an uncommon event, occurring due to the infarction and/or haemorrhage usually of a previously unknown pituitary adenoma. It can occur in all adenoma subtypes but is more common in nonfunctioning pituitary adenomas. The physiopathology is not completely clear, and precipitating factors, such as major surgeries, anticoagulant use or pituitary dynamic tests, can be found in up to 40% of patients. The clinical presentation is characterized by a rapid onset with a headache as the main symptom, but visual disturbances can also be present as well as meningism and intracranial hypertension. The diagnosis is based on imaging evaluations, mainly using magnetic resonance imaging, which can show various patterns depending on the timeframe following the occurrence of the apoplectic event. Pituitary hormonal deficits are also common, and the evaluation of hormonal levels is mandatory. Pituitary apoplexy can be managed by surgery or conservative treatment, and a multidisciplinary team is essential for the decision-making process. The outcome is usually positive with both surgical and conservative approaches, but surveillance is needed due to the risk of re-bleeding or tumour recurrence.

Viral meningitis is mainly caused by non-polio enteroviruses (NPEV). Large-scale data on the clinical characteristics between different outbreaks within the same region are lacking. This study aimed to analyse a possible influence of the circulating NPEV genotype on the disease outcome of affected children. A retrospective cohort study analysing two major outbreaks of NPEV meningitis in Germany in 2008 and 2013 was conducted in cooperation with the National Reference Centre for Poliomyelitis and Enteroviruses (NRC PE) and five German children's hospitals. A total of 196 patients with laboratory-confirmed NPEV meningitis were enrolled. In 2008, children with NPEV meningitis had significantly higher fever and showed more behavioural changes and less back pain. To better define typical findings in echovirus 30 (E-30) meningitis, patients were split into the following three groups: E-30 positive patients, patients with "Non E-30" infection and patients with "Untyped" NPEV infection. E-30 positive patients were significantly older and their disease course was more acute, with early admission to but also early discharge from hospital. E-30 positive patients showed a significantly higher rate of headache and meningism, and a lower rate of diarrhoea and clinically defined septicaemia when compared to the others. Regarding laboratory testing, E-30 positive patients presented with significantly elevated peripheral blood neutrophil counts when compared to patients with "Non E-30" or "Untyped" NPEV infection. In conclusion, E-30 meningitis in children shows a characteristic pattern of clinical features. To further characterise NPEV strains worldwide, continuous surveillance and typing of NPEV strains causing central nervous system disease is warranted.

Background The symptoms of meningitis which include fever, headache, photophobia and irritability along with abducens nerve palsy pose a diagnostic dilemma requiring urgent attention. Here we report how such a dilemma was methodically and sequentially resolved using anatomical knowledge supported by neuroimaging and the eventual diagnosis of Gradenigo syndrome was made. Case presentation A 6-year-old previously healthy boy from Sri Lanka presented with high grade fever, headache, photophobia and left eye pain for 10 days and diplopia for 2 days duration. Neurological examination was unremarkable except for left sided abducens nerve palsy. He had high inflammatory markers and white blood cell count. A tentative differential diagnosis of acute bacterial meningitis complicated by cerebral oedema, acute hydrocephalus or cerebral abscess was made. However, non-contrast CT brain, cerebrospinal fluid analysis and electroencephalogram were normal leading to a diagnostic dilemma. MRI brain with contrast performed 3 days later due to limited resources revealed left mastoiditis extending to petrous temporal bone confirming Gradenigo syndrome. Conclusion This case report highlights the importance of a thorough physical examination in children presenting with unrelated neurological symptoms and signs. Unilateral abducens nerve palsy raises the suspicion of increased intracranial pressure and neuroimaging is vital in diagnostic uncertainties. Gradenigo syndrome emphasises the importance of incorporating anatomical knowledge into clinical practice.

Subarachnoid hemorrhage is a serious and life-threatening medical condition which commonly presents with an acute headache. Unfortunately, it remains frequently misdiagnosed at initial presentation with dire consequences in terms of patient morbidity and mortality. The goal of this paper is to review salient features in the clinical history, as well as recently developed clinical decision rules, which can help determine which patients warrant further investigation for subarachnoid hemorrhage when the initial presentation is that of an acute headache. A recent prospective observational study showed that occipital location, stabbing quality, presence of meningism, and onset of headache during exertion were characteristics in the clinical history that can distinguish the headache of SAH from other causes. The Ottawa headache rule is a clinical decision tool which was developed to help identify patients presenting to the ED with acute non-traumatic headache who require investigation to rule out subarachnoid hemorrhage. Using this tool, it is recommended that patients who meet any one of the following 6 criteria are investigated further: Onset greater than or equal to 40 years, presence of neck pain or stiffness, witnessed loss of consciousness, onset during exertion, thunder clap headache (pain peaking within 1 s), or limited neck flexion on exam. An informed and thoughtful approach that takes into account the timing, presentation, risk factors, and resources, as discussed here, should help distinguish between the patient that warrants further evaluation and intervention for SAH and one who does not. The Ottawa SAH rule is a useful clinical decision tool for young inexperienced clinicians in order to avoid missed diagnoses. However, its clinical value is limited by its low specificity. Clinical decision tools with higher specificity are needed.

The cardinal symptoms of bacterial meningitis are headache, fever, impaired consciousness and nuchal stiffness (meningism); however, the diagnosis of acute bacterial meningitis can only be confirmed or ruled out by investigation of cerebrospinal fluid. The recommended empirical antibiotic regimen for community-acquired acute bacterial meningitis in adults in Germany is a combination of ceftriaxone and ampicillin plus adjuvant dexamethasone. An important influenceable factor for treatment success of acute bacterial meningitis is a rapid induction of antibiotic therapy, which must be initiated directly after lumbar puncture. When this is delayed for any reason, e. g. because of the necessity of cerebral computed tomography imaging before lumbar puncture, antibiotics should be started even before acquisition of cerebrospinal fluid.

Background Defined by an infection of the ventricular system of the brain, ventriculitis is usually known as a health-care associated infection. In contrast, primary pyogenic ventriculitis complicating community-acquired meningitis is uncommon, and mainly described in infants. Only seven cases that have occured in adults have been found in the international literature. Case presentation We report here a new case due to Neisseria meningitidis occurring in an 85 year-old-man. The comparison with previous reports allows to drawn several conclusions: (i) cases occurred in relatively old adults (median age: 65 years); (ii) Streptococcus pneumoniae, N. meningitiditis and Staphylococcus aureus are the leading responsible pathogens; (iii) atypical clinical presentation seems the rule in which meningism often lacks; (iv) in absence of clinical or biological specific parameters, modern brain imaging such as magnetic resonance imaging with gadolinium enhancement is of utmost importance for the diagnosis, leading to anticipate an increase of the diagnosis in the near future, thanks to easier access to such exploration; (v) death or serious sequelae commonly occurred; (vi) prolonged antibiotic courses (6 weeks to 3 months) have been used, without strong rational. In the given case, the patient presented with a lack of meningeal irritation signs. The diagnosis was made by MRI considering a lasting confused state. A four-week antibiotic regimen was successful, combining two weeks of intravenous cefotaxime followed by two weeks of oral levofloxacin much easier to administrate and allowing early rehabilitation. Conclusion Primary bacterial ventriculitis is a real diagnosis challenge. Larger indications of MRI for bacterial meningitis, particularly in cases with an atypical presentation or poor evolution would certainly increase the number of diagnosis.

Headache after aneurysmal subarachnoid hemorrhage (SAH) is very common and is often described as the “worst headache imaginable.” SAH-associated headache can persist for days to weeks and is traditionally treated with narcotics. However, narcotics can have significant adverse effects. We hypothesize that gabapentin (GBP), a non-narcotic neuropathic pain medication, would be safe and tolerable and would reduce narcotic requirements after SAH. We retrospectively reviewed the clinical, radiographic, and laboratory data of SAH patients at the neuroscience intensive care unit at Mayo Clinic in Jacksonville, Florida, from January 2011 through February 2013. Headache intensity was quantified by a visual analog scale score. Total opioid use per day was tabulated using an intravenous morphine equivalents scale. Cerebrospinal fluid was also reviewed when available. There were 53 SAH patients who were treated with GBP along with other analgesics for headache. Among these SAH patients, 34 (64 %) were women, with a mean age of 54 years (SD 12.3). Severe headache was observed in all SAH patients. GBP dosing was rapidly escalated within days of SAH up to a median of 1,200 mg/day, with a range of 300 mg three times a day to 900 mg three times a day. Approximately 6 % of patients treated with GBP had nausea (95 % CI 1–16 %), and only one patient (1.8 %) had to discontinue GBP. GBP appears to be relatively safe and tolerable in SAH patients with headache and may be a useful narcotic-sparing agent to prevent narcotics-associated complications, such as gastrointestinal immobility, ileus, and constipation.

Dear Sir,A 38-year-old female presented with a 4-day history ofacute onset of headache, fever of 40 C, and generalizedfatigue at a peripheral hospital. The patient presented noneurological deficits, especially no signs of meningism,and the remaining examination was normal. The CRPwas increased (192 mg/l, normal \5 mg/l). Creatinine(1.03 mg/dl) and blood urea nitrogen (38.0 mg/dl) werenormal. The cranial CT scanning excluded subarachnoidhemorrhage. A cranial MRI excluded cerebral venous sinusthrombosis, but showed a hyperintense lesion in the sple-nium of the corpus callosum (Fig. 1a–c). The patient wastransferred to the university hospital. A lumbar puncturecould not be performed at that time, due to thrombocyto-penia and abnormal coagulation (platelets 51 9 10

The incidence of tuberculosis (TB) is increasing in both developing and developed worlds, and children, in particular, represent a high-risk group for acquiring the disease. TB of the central nervous system is the most severe, life-threatening form of TB in infants and children. Approximately 10% of all patients with TB have central nervous system involvement.We have selected four pediatric cases of unusual spinal TB that presented to our institution during the last 5 years. These include TB arachnoiditis, intramedullary spinal cord tuberculoma, TB spondylitis of the odontoid peg, and one child with tuberculous extradural abscess.TB may involve the intramedullary, extramedullary intrathecal compartment, or the extrathecal vertebral compartment in the form of an arachnoiditis, abscess, and spondylitis, respectively, often with unusual imaging presentations.

We report three patients who presented with occipital headache, neck pain, meningism, fever, and inflammatory findings in laboratory tests. Lumbar puncture for suspected meningitis revealed normal CSF findings in all patients. Magnetic resonance imaging demonstrated inflammation of the deep neck space, leading to the final diagnosis of retropharyngeal abscess.

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrenees atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Fusobacterium necrophorum, an anaerobic, gram-negative rod, belongs to the physiological flora of the oropharynx. It causes Lemierre's syndrome characterized by oropharyngeal infection, septic thrombophlebitis of the neck, in particular of the internal jugular vein, and metastatic abscesses, predominantly in the lungs. Rarely, and mainly in children, it causes meningitis. Here we report the clinical course of a 25-year-old woman with F. necrophorum meningitis. She presented with incomplete, right third nerve palsy. Within a few days, she developed fever, meningism and progressive reduction of vigilance. Cerebrospinal fluid analysis showed typical signs of bacterial meningitis. After the identification of F. necrophorum, the antibiotic treatment was changed to meropenem, which led to continuous improvement of the clinical symptoms. Due to persistent signs of inflammation in the CSF, metronidazole was added to the antibiotic regime. This case report demonstrates that F. necrophorum should always be considered in the diagnostic workup of bacterial meningitis in adults.

We report on a 70-year-old female with acute onset of headache, meningism, xanthochromic cerebrospinal fluid, and developing laboratory parameters indicating a systemic infection. Initially, a subarachnoidal hemorrhage was assumed. However, magnetic resonance imaging showed upper cervical osteomyelitis and extending spinal epidural abscess. After application of broad systemic antibiotics, secluded abscess formation was achieved and successful neurosurgical debridement performed. The unusual cranial concentration of the complaints is probably due to the involvement of the craniocervical transition. Cervical epidural spinal abscess represents a potentially dangerous bacterial infection of the upper spine. Inadequate treatment can lead to irreversible neurological deficits. Cervical magnetic resonance imaging is an effective tool for diagnosis, since early diagnosis is important for good prognosis.

In most cases a saccular aneurysm is the cause of acute subarachnoidal hemorrhage (SAH). The usual symptoms are severe headache and meningism. Due to the high mortality rate caused by rebleeding an early occlusion of the aneurysm should be strived for. For this early diagnosis an exact identification of the aneurysm and its configuration is essential.

CNS-Toxocarosis is a rare clinical manifestation of Toxocara canis or Toxocara catis infection. Commonly, blood or CSF-eosinophilia directs investigations towards a parasitic origin of the syndrome. We describe a patient with severe eosinophilic meningoencephalomyelitis due to a Toxocara infection. A 44-year-old woman (dog owner) was admitted to a hospital due to a probable epileptic seizure and increasing headache. CSF-analysis revealed mild lymphomonocytic pleocytosis (86 leucocytes/ll), elevated protein levels (1,410 mg/l) and mildly elevated CSF-lactate (2.94 mmol/ l). The patient was treated with ceftriaxone, ampicillin and aciclovir (until negative HSV-PCR testing was confirmed). Six days later, she developed fever (41 C) and signs of myelopathy with paraparesis, sensory loss below TH4 and urinary retention. She was transferred to our hospital as psychomotorically slowed, with intermittent disturbances of consciousness, slight meningism and paraplegia of the legs without pyramidal signs, normal muscle tendon reflexes, diminished anal sphincter tonus and severe sensory loss below TH6. Spinal MRI revealed signs of myelitis (Fig. 1) while cerebral MRI was normal except for a slight leptomeningeal enhancement. CSF-analysis 2 weeks after symptom onset showed lymphomonocytic pleocytosis (51/ ll) and 10% eosinophilic granulocytes. Lactate was 4.72 mmol/l, protein (935 mg/l) and serum/CSF-albumin ratio were elevated (19.2, normal \7), CSF-glucose concentration was 55% of serum-glucose. CSF-IgM index was 1.1 (normal \0.2), IgA and IgG indices were normal. No eosinophilia was found in peripheral blood. Extensive microbiological workup was negative for all herpesviridiae, HIV, FSME, HHV6, LCMV, HTLV1, poliomyelitis, neurosyphilis, neuroborreliosis, neurotuberculosis, brucellosis, toxoplasmosis, listeriosis, ascaridosis, cysticercosis, filariosis or infections with chlamydia or mycoplasma-species. Vasculitis and sarcoidosis screening was unremarkable. An oncologic disorder was ruled out by whole-body PET/CT. Toxocara IgG-ELISA (sensitivity 91–95%, specificity 86–93%) and Western blot were positive in peripheral blood (35 antibody units) and CSF (65 antibody units) [1]. Treatment with dexamethasone (3 9 8 mg/day) led to marked improvement with the patient being fully oriented, awake, and remission of the paraplegia to a MRC 2–3 paraparesis. Tapering of dexamethasone to 2 mg/day worsened the paraparesis resolving again under high-dose methylprednisolone (1 g/day for 5 days), thereafter continued with 1 mg/kg body weight/day for several weeks. O. C. Singer (&) K. Jahnke H. Steinmetz Department of Neurology, Goethe-University, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany e-mail: o.singer@em.uni-frankfurt.de

Histoplasma capsulatum is endemic in parts of Africa, Asia, the United States, and Latin America. Most infections are benign and self-limiting, but disseminated disease can occur in immunocompromised patients, particularly in the setting of HIV infections [3]. Central nervous system (CNS) involvement is found in 5–10% of cases of disseminated histoplasmosis [6], but isolated CNS histoplasmosis is rare. Here we present an unusual case of recurrent granulomatous disease of the CNS and epiglottis in an immunocompetent adult due to histoplasmosis. A 46-year-old Ugandan woman, who came to England in her teens, presented in 2001 with progressive headaches, vomiting, meningism and confusion. Recent travel history was limited to North American and European cities. Chest X-ray and MRI of the brain were normal. Cerebrospinal fluid (CSF) examination revealed 350 lymphocytes, 1.19 g/l protein and 2.3 mmol/l glucose (6 mmol/l plasma), and negative culture. She was treated for probable tuberculous meningitis with dexamethasone and anti-tuberculous therapy for 12 months. Her condition improved significantly although repeat MRI of the brain in 2002 showed abnormal leptomeningeal enhancement around the pons and occipital sulci. She developed hydrocephalus in 2003, necessitating insertion of a ventriculo-peritoneal shunt. She remained well until 2004 when she developed dysphonia. Laryngoscopy detected an epiglottic mass with non-caseating granulomata on biopsy. No mycobacteria were seen. Two subsequent biopsies confirmed the findings. Whole body fluorodeoxyglucose PET in 2005 revealed increased laryngeal uptake. She received courses of high dose oral steroids for probable epiglottic sarcoidosis with partial clinical response. She presented to us in December 2006 with worsening dysphonia, spastic paraparesis, sensory deficit to the T8 level and urinary retention. Blood tests including inflammatory markers, autoantibodies, angiotensin converting enzyme and HIV serology were normal or negative. MRI showed diffuse meningeal enhancement around the brainstem and entire spinal cord but no intramedullary lesions. CSF examination showed normal opening pressure, 44 mononuclear cells, 2.5 mmol/l glucose (8.1 mmol/l plasma), 3.44 g/l protein, and intrathecal synthesis of oligoclonal bands. She was treated empirically with high dose steroids and anti-tuberculous therapy (rifampicin, isoniazid, pyrazinamide and ofloxacin). Her condition continued to decline with ascending weakness and sensory deficit (T1 level). MRI in January 2007 showed more extensive meningeal enhancement and intramedullary nodules of enhancement in the cervical cord and medulla (Fig. 1). CSF examination showed 180 polymorphs, 0.2 mmol/l glucose (6.6 mmol/l plasma) and 12.3 g/l protein. CSF culture and PCR for mycobacteria were negative. Serum brucella and histoplasma antibodies and aspergillus precipitins were negative. Laryngeal biopsy showed non-caseating granulomata with no organisms. Protionamide was added for possible resistant tuberculosis. Her condition did not improve and intravenous liposomal amphotericin B was initiated to cover granulomatous fungal infection. Y. F. Tai (&) D. M. Kullmann R. S. Howard N. P. Hirsch T. Revesz S. M. Leary National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK e-mail: yen.tai@imperial.ac.uk

A 57-year-old male caucasian patient presented with a mild, dull left sided headache lasting for several weeks. Additionally, the patient complained about moderate memory deficits. Approximately 1 week before admission there had been increase in headache intensity. Previous medical history was unremarkable. Neurological examination did not reveal meningism or any focal neurological deficits. Fever was absent and blood tests were normal. T2-weighted MRI showed a hyperintense left hemispheric lesion, affecting the anterior temporal lobe, insula and inferior frontal lobe (Fig. 1). Pathological contrast enhancement appeared in the anterior temporal lobe adjacent to the sylvian fissure. CSF analysis revealed lymphocytic pleocytosis with 177 cells/ll and an elevated protein level (61 mg/dl). Electroencephalography (EEG) showed a mild left temporal slowing without detection of epileptic discharges. Under the suspicion of viral encephalitis, antiviral therapy with intravenous acyclovir was initiated. Neuropathological examination of tissue obtained from a stereotactic brain biopsy ruled out a tumor and revealed inflammatory changes. Despite the mild clinical course, the MRI, CSF, biopsy and EEG findings were suspicious of HSE. Yet, prior to acyclovir treatment, CSF analysis by polymerase chain reaction (PCR) performed shortly after admission and therefore at least 1 week after disease onset, did not detect herpes simplex virus (HSV) DNA. In addition, extensive serological, microbiological and virological analyses of CSF were negative. There were no indications of an underlying (immunosuppressive) condition. Under treatment with intravenous acyclovir (750 mg tid) for 12 days, there was remission of inflammatory CSF changes (24 cells/ll) and follow-up MRI showed a decrease of the left temporal lesion and contrast enhancement. The patient was discharged home with only mild memory deficits, without headache. Eighteen months later, the patient presented with practically the same complaints: again, there was a mild headache present for some weeks, this time more pronounced on the right side. The medical history during N. Peters (&) D. Theil T. Birnbaum S. Noachtar Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377 Munich, Germany e-mail: Nils.Peters@med.uni-muenchen.de

Herpes simplex virus (HSV) typically causes mucocutaneous disease, encephalitis, and acute men ingitis. There have been no previous reports of chronic meningitis due to this virus. A case of chronic meningitis due to herpes simplex virus type 2 (HSV-2) in a previously healthy 35-year-old woman whose predominant symptoms were headache and meningism without fever is described. Analysis of cerebrospinal fluid (CSF) revealed a lymphocytic pleocytosis, elevated protein, and hypoglycorrhachia. The diagnosis of herpes simplex meningitis was supported by the detection of HSV-2 DNA in CSF by polymerase chain reaction and by intrathecal production of HSV-specific antibody. The patient recovered after treatment with intravenous acyclovir and glucocorticoids.

The purpose of this report is to describe a new complication of propofol administration. A previously fit patient underwent intravenous anaesthesia with propofol for removal of dental wires. Postoperatively he developed myoclonic jerking of his limbs. On regaining consciousness he complained of an occipital headache, neck stiffness and photophobia, and was found to have nuchal rigidity on examination. These clinical features resolved over the following week. Subsequent investigations failed to explain the aetiology of the symptoms of meningeal irritation, which suggests that propofol was the causative agent. While prolonged myoclonus has been previously described with propofol administration, this is the first report of meningism occurring with its use.

We read with interest the review by Antonio Tristano [1] regarding neurological adverse events associated with antitumour necrosis factor alpha (anti-TNF-a) treatment. We believe that aseptic meningitis is also a potential complication of anti-TNF-a treatment and we report the following case. A 53-year-old plumber presented with 3 weeks of night sweats, fevers and generalised headache. There was no weight loss, recent foreign travel, occupational exposure to sewage or chemicals. He had a single female sexual partner and a recent negative human immunodeficiency virus (HIV) test. He had a pet dog and no further contact with animals or insect bites. His past history included IgA nephropathy (currently quiescent), hypothyroidism and an undifferentiated seronegative inflammatory arthritis. This had involved generalised joint pains but had particularly involved his right ankle and a biopsy had shown synovitis. He was HLA B27 negative. He had been treated with sulphasalazine, which was not tolerated. Despite methotrexate and oral steroids he had continuing right subtalar joint inflammation and adalimumab was added. At presentation his disease was inactive. His medications were levothyroxine, Humira (adalimumab) 40 mg/week since 2008 and oral methotrexate 20 mg/week since 2007 and his arthritis symptoms were well controlled. He was not taking non-steroidal antiinflammatory medication, and took paracetamol (acetaminophen) only for his headache. On admission, examination revealed a pyrexia, \5 splinter haemorrhages, normal heart sounds, chest, abdomen, neurological examination and no meningism, lymphadenopathy or oro-genital ulceration. Investigations showed white cell count 12.7 9 10/L (reference range 3.8–10.6 9 10/L), neutrophil count 9.16 9 10/L (reference range 1.8–6.5 9 10/L), monocyte count 1.12 9 10/L (reference range 0.2–0.8 9 10/L) with C-reactive protein, lactate dehydrogenase and blood film normal. IgA was mildly elevated at 4.11 g/L (reference range 0.8–4.0 g/L). Liver, renal, and thyroid function, plasma viscosity, creatinine kinase, chest X-ray and unenhanced MRI brain/ enhanced MRI spine were normal. Three sets of blood cultures were negative. Urinalysis including Bence-Jones protein and a myeloma screen were negative. Two urine specimens and a sputum specimen were also negative for auramine-phenol stain and tuberculosis (TB) culture after 6 weeks. Complement, extractible nuclear antigens, lupus anticoagulant, anticardiolipin antibody, double stranded DNA and antinuclear antibody were negative. Classical anti neutrophil cytoplasmic antibody (cANCA) was positive (titre 1:320), MPO and PR-3 negative. Cerebrospinal fluid (CSF) was measured serially (see Table 1). Oligoclonal bands were negative. A cytospin with immunophenotyping showed evidence of lymphocyte infiltration, the lymphocyte population consisting of both B and T cells. Cytology revealed reactive lymphocytes. Auramine-phenol stain for TB and TB culture was negative. Cryptococcal antigen and fungal cultures were negative after extended incubation. Herpes simplex virus DNA, enterovirus RNA and CMV (via PCR) were not detected. A CT scan of the thorax/abdomen/pelvis and trans-thoracic echocardiography were normal. HIV and hepatitis A. J. Hamilton (&) N. J. Gutowski Department of Neurology, Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon EX2 5DW, UK e-mail: alexander.hamilton@nhs.net

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially life-threatening drug reaction which usually occurs after exposure to aromatic antiepileptics. AHS secondary to non-aromatic antiepileptics is even more rare and there are only few case reports of AHS presenting as aseptic meningitis. We present the case of a 48-year-old patient who presented with meningism within 3 weeks of adding lamotrigine for control of her juvenile myoclonic epilepsy. When lamotrigine was restarted 2 weeks later she developed similar but more severe symptoms which resolved on stopping lamotrigine. Our patient was subsequently rendered seizure free on levetiracetam which has not so far been linked with this syndrome. It is important to be aware of this life-threatening complication associated with the use of antiepileptics.

Sirs: In a clinical setting, isolated thunderclap headache is commonly assumed to be benign in origin once subarachnoid haemorrhage (SAH) has been excluded [1]. However, cerebral venous sinus thrombosis (CVST) is an infrequent, alternative cause of sudden-onset headache and is not conclusively excluded by normal conventional CT and LP. CVST is also a recognised rare cause of SAH. Here, we report a case of CVST presenting with thunderclap headache and complicated by delayed SAH. A previously well 53-year-old woman presented with spontaneous, sudden-onset occipital headache as her sole symptom. Neurological examination including fundoscopy was normal, with no evidence of meningism. Acute head CT and subsequent LP performed 16 hours after onset were unremarkable (opening pressure 19 cm, CSF acellular with no bilirubin detectable on spectrophotometry). The headache resolved completely within 24 hours and the patient was discharged with a diagnosis of primary thunderclap headache. The following day, she represented with sudden-onset headache at rest accompanied by mild neck stiffness. Her symptoms resolved before a further suddenonset headache occurred two days later. Examination remained normal throughout. Repeat, unenhanced head CT demonstrated a small, high left frontal SAH along the cranial convexity without involvement of the basal cisterns (Fig. 1a). CT angiography detected no arterial aneurysm, but its venous phase showed changes suggestive of superior sagittal sinus thrombosis, which was confirmed on MR venography (Fig. 1b). Screening for secondary causes of thrombosis was negative. She was initially treated with intravenous unfractionated heparin to allow rapid reversal in case of rebleeding, before being warfarinised under cover from low molecular weight heparin. She remained well at follow-up six months later. Repeat MR angiography showed resolution of the superior sagittal sinus thrombosis, with no other vascular or brain parenchymal abnormalities. Thunderclap headache is an unusual presentation of CVST, perhaps seen in fewer than 20 % of cases [2]. Rarely, there may be no concomitant findings to suggest the presence of a CVST, such as focal neurological signs, seizures or features of raised intracranial pressure. Most patients with CVST have a raised opening pressure and abnormal CSF constituents, but absence of these features does not conclusively rule out the diagnosis. In a previous series of 38 cases, nine patients had both opening pressure and CSF constituents measured, and in one of them all parameters were normal [3]. SAH is a very rare complication of cerebral venous thrombosis, with only 30 cases reported to date. It has been suggested that venous intraparenchymal haemorrhages may rupture into the subarachnoid space, thus causing sudden-onset headache in CVST [2, 4]. However, we hypothesise that our patient’s first headache was caused by the CVST, as there was no evidence of SAH on initial brain CT and bilirubin was not detectable in the CSF. The second or third episode of headache may have been caused by SAH. LETTER TO THE EDITORS

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

A retrospective study of the medical records of 115 consecutive cases of meningococcal disease with 11 fatalities was carried out in order to evaluate the power of 15 clinical and laboratory variables available on admission in predicting a fatal outcome. On linear discriminant analysis, six variables showed a significant discriminating power in predicting death: low systolic blood pressure, low platelet count, extensive petechiae, high body temperature, low CSF polynuclear cell count and absence of meningism. From a stepwise linear discriminant analysis, two alternative procedures for prognostic evaluation were derived. If a large high risk group is accepted which will include practically all patients at risk of death, a prognostic evaluation based only on systolic blood pressure on admission is sufficient. Alternatively, if unconventional, potentially hazardous therapy is considered for high risk patients, a small high risk group may be defined. Patients with systolic blood pressure less than 100 mm Hg, platelet count less than or equal to 125 X 10(9)/l and body temperature greater than 39 degrees on admission constitute a small group with a very high mortality. A similar risk group was defined if platelet count less than or equal to 125 X 10(9)/l was substituted for extensive petechiae. The advantage of the latter procedure is that only a simple bedside examination is required for the prognostic evaluation.

The French Club of Pediatric Intensive Care has prospectively studied 90 cases of infectious purpura which were hospitalized in 1981; the purpose of this study was to determine prognostic factors. The statistical study (X2 test) of all these cases is in agreement with data in the literature and shows that the mortality is significantly higher when there is: shock (p less than 0.001), coma (p less than 0.05), ecchymotic or necrotic purpura (p less than 0.01), temperature less than 36 degrees C (p less than 0.05), no clinical meningism (p less than 0.001), white cell count less than 10,000/mm3 (p less than 0.05), thrombocytopenia less than 100,000 (p less than 0.01), fibrinogen less than 1.5 g/l (p less than 0.001), kalemia greater than 5 mEq/l (p less than 0.01), spinal fluid cell count less than 20/mm3 (p less than 0.01). Because shock is one of the main prognostic factors (23 deaths in 55 shocked patients, versus 2 in 35 non-shocked) we have performed another statistical study (with the Benzecri method) to determine a prognostic index for patients in shock. For its determination, five initial parameters are used: age, kalemia, white cell count, clinical meningism, platelet count. The predictive value for survival is 91%. The predictive value for death is 87%. The score was applied on the patients hospitalized in shock in 1982: the predictive value for survival is 75%, the predictive value for death is 61%.

During 1960 the West of Scotland experienced a large outbreak of ECHO 9 infection. ECHO 9 virus strains were readily recovered from faeces, cerebrospinal fluids and throat swabs. Results of the comparison of human amnion and rhesus monkey kidney tissue cultures for the isolation of ECHO 9 suggested that monkey kidney was more sensitive than human amnion.

The amylase activity in C.S.F. of normal subjects was much lower than the corresponding serum values, and ranged between 6.5 and 9.5 SU per 100 ml. The amylase activity of C.S.F. from cases of meningism was slightly raised above the normal, but the difference was not significant. The C.S.F. from cases of tuberculous and septic meningitis showed markedly elevated amyloclastic activity with average values of 65.5 SU and 186.3 SU per 100 ml. respectively.