Rotavirus meningitis in an adult with transient aphasia.

We identified an additional case of documented Rotavirus meningitis in an adult with full medical history. A previously healthy 37-year-old patient presented herself for transient aphasia associated with fever and headaches at the end of a one-week history of gastroenteritis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic meningitis, and treatment with aciclovir was initiated. Rotavirus A reverse transcription-polymerase chain reaction (RT-PCR) was positive in CSF and the patient's stools in favor of Rotavirus meningitis. Testing for other viruses was negative. Magnetic resonance imaging (MRI) showed no signs of encephalitis. Aphasia was resolutive in less than 12 hours, and no neurological symptoms relapsed. All symptoms evolved favorably despite aciclovir discontinuation. Viral sequencing methods have recently identified unexpected viruses as potential causative agents in meningitis, including Rotavirus. We confirm the detectability of Rotavirus in the analysis of CSF in the context of Rotavirus gastroenteritis in an adult. This case suggests postviral headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome may be linked to previously undetected direct viral infection of the central nervous system. Therefore, clinicians should consider Rotavirus meningitis in diagnosing meningitis associated with gastroenteritis in adults.

Bilateral cavernous sinus thrombosis complicating acute unilateral pansinusitis in a 15-year-old boy.

Cavernous sinus thrombosis (CST) is a rare and potentially fatal complication of acute sinusitis. Timely diagnosis and management is, therefore, essential in preventing death and neurological disability. Here, we describe the case of a paediatric patient with bilateral CST secondary to acute unilateral pansinusitis that presented with rapidly progressing bilateral periorbital oedema. Initial imaging was negative. This case serves to emphasise the importance of maintaining a high index of suspicion when managing paediatric patients with suspected CST with persistent symptoms. Expeditious investigation and management of our patient in this case resulted in a positive outcome, with resolution of symptoms and no residual neurological deficit.

Isolated intracranial hypertension associated with COVID-19.

BACKGROUND: Headache is a frequent complaint in COVID-19 patients. However, no detailed information on headache characteristics is provided in these reports. Our objective is to describe the characteristics of headache and the cerebrospinal fluid (CSF) profile in COVID-19 patients, highlighting the cases of isolated intracranial hypertension. METHODS: In this cross-sectional study, we selected COVID-19 patients who underwent lumbar puncture due to neurological complaints from April to May 2020. We reviewed clinical, imaging, and laboratory data of patients with refractory headache in the absence of other encephalitic or meningitic features. CSF opening pressures higher than 250 mmH2O were considered elevated, and from 200 to 250 mmH2O equivocal. RESULTS: Fifty-six COVID-19 patients underwent lumbar puncture for different neurological conditions. A new, persistent headache that prompted a CSF analysis was diagnosed in 13 (23.2%). The pain was throbbing, holocranial or bilateral in the majority of patients. All patients had normal CSF analysis and RT-qPCR for SARS-CoV-2 was negative in all samples. Opening pressure >200 mmH2O was present in 11 patients and, in six of these, > 250 mmH2O. 6/13 patients had complete improvement of the pain, five had partial improvement, and two were left with a daily persistent headache. CONCLUSIONS: In a significant proportion of COVID-19 patients, headache was associated to intracranial hypertension in the absence of meningitic or encephalitic features. Coagulopathy associated with COVID-19 could be an explanation, but further studies including post-mortem analysis of areas of production and CSF absorption (choroid plexuses and arachnoid granulations) are necessary to clarify this issue.

Listeria rhombencephalitis mimicking acute disseminated encephalomyelitis in a patient without predisposing medical conditions.

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.

Diagnostic test accuracy of jolt accentuation for headache in acute meningitis in the emergency setting.

BACKGROUND: Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes. Inflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely. Jolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy. OBJECTIVES: To estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020. SELECTION CRITERIA: We included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy. DATA COLLECTION AND ANALYSIS: Two review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children. The reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid. Risk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup. Overall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome). Amongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence). AUTHORS' CONCLUSIONS: Jolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research.

To handle the HaNDL syndrome through a case: The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis.

The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity. This disease has been related to migrainous headaches. It is a benign, self-limited disorder, which is characterized by fluctuating neurological symptoms and cerebrospinal fluid lymphocytosis. We describe a case of a 47 years old man with acute onset of headache and aphasia. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis (25 cells/µl, 100% lymphocytes). Electroencephalogram showed moderate slow rhythm in the left hemisphere, with temporoparietal predominance, and without epileptiform activity. His blood tests as well as magnetic resonance imaging (MRI) results were normal. With the diagnosis of HaNDL syndrome the patient was accepted in the Department of Neurology and discharged with full recovery.

Predictors of hospital discharge outcome from the presenting clinical characteristics and the first cerebrospinal fluid analysis among the patients with cryptococcal meningitis.

OBJECTIVE: Prognosticators of the outcome of patients with cryptococcal meningitis (CM) at variable follow-up time has been reported. We aimed to identify prognosticators of an outcome on hospital discharge of treated CM. PATIENTS AND METHODS: The presenting characteristics of CM patients admitted in Songklanagarind Hospital from 2002 to 2017 were retrospectively reviewed. The unfavorable outcome was defined as no improvement or death after starting treatment. The significant differences in clinical presentations between the patients with favorable and unfavorable outcomes were descriptively analyzed. The significant independent predictors from the clinical presentations and the first results of cerebrospinal fluid (CSF) analysis with cut-off values were further defined by multiple logistic regression analysis and shown in adjusted odds ratios (p < 0.05). RESULTS: Sixty-two CM patients were enrolled and 33 (53.2%) of them were females. Their median (IQR) age was 37 (30, 46) years old. HIV serology was positive in 71.0%. Concurrent immunosuppressant use and systemic malignancies were 6.5 and 4.8%, respectively. The median (IQR) days of hospital stay was 18.0 days (12.8, 23.0). Eleven patients had unfavorable outcomes at hospital discharge (8 died, 3 no neurological improvement). Cranial nerve palsy and high CSF protein were dependent predictors for the unfavorable outcome, while high CSF glucose was a protective factor. In addition, CSF protein >270 mg/dL was an independent predictor for the unfavorable outcome when adjusted for other CSF analysis results (adjusted odds ratio 27.1, 95% confidence interval 1.1-678.5, p = 0.034). CONCLUSION: Elevated CSF protein was a significant independent predictor for an unfavorable outcome.

Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) in a patient with confusional symptoms, diffuse EEG abnormalities, and bilateral vasospasm in transcranial Doppler ultrasound: A case report and literature review. / Síndrome de cefalea transitoria con déficits neurológicos asociados y pleocitosis en líquido cefalorraquídeo (HaNDL) con cuadro confusional, EEG compatible con afectación difusa y datos de vasoespasmo bilateral en estudio Doppler transcraneal: presentación de un caso y revisión de la literatura.

INTRODUCTION: HaNDL syndrome (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) is characterised by one or more episodes of headache and transient neurological deficits associated with cerebrospinal fluid lymphocytosis. To date, few cases of HaNDL manifesting with confusional symptoms have been described. Likewise, very few patients with HaNDL and confusional symptoms have been evaluated with transcranial Doppler ultrasound (TCD). TCD data from patients with focal involvement reveal changes consistent with vasomotor alterations. DEVELOPMENT: We present the case of a 42-year-old man who experienced headache and confusional symptoms and displayed pleocytosis, diffuse slow activity on EEG, increased blood flow velocity in both middle cerebral arteries on TCD, and single-photon emission computed tomography (SPECT) findings suggestive of diffuse involvement, especially in the left hemisphere. CONCLUSIONS: To our knowledge, this is the first description of a patient with HaNDL, confusional symptoms, diffuse slow activity on EEG, and increased blood flow velocity in TCD. Our findings suggest a relationship between cerebral vasomotor changes and the pathophysiology of HaNDL. TCD may be a useful tool for early diagnosis of HaNDL.

Optic neuritis caused by the re-emerging great masquerader.

A 49-year-old Caucasian woman presented with subacute headache and right eye pain associated with scotoma, blurred vision and photophobia. MRI was suggestive of optic neuritis of the right optic nerve and she was treated with steroids. Due to persistent symptoms, a lumbar puncture was performed and cerebrospinal fluid analysis was positive for venereal disease research laboratory and rapid plasma reagin titres. On further history, she recalled experiencing an illness associated with diffuse rash, likely secondary syphilis, 1-2 months prior. She tested negative for HIV. She was treated with intravenous penicillin for 2 weeks following which she experienced improvement in symptoms.

Does This Adult Patient With Jolt Accentuation of Headache Have Acute Meningitis?

OBJECTIVE: In order to identify appropriate candidates with suspected meningitis for lumbar puncture (LP), study designs and diagnostic values of jolt accentuation of headache (JA) were reviewed. BACKGROUND: Acute meningitis is a life-threatening disease that requires LP for accurate diagnosis. JA was reported the most sensitive indicator of cerebrospinal fluid pleocytosis; however, subsequent studies have failed to confirm this claim. METHODS: We reviewed articles concerning JA, published prior to December 2017, using MEDLINE and Japanese medical databases. Seven original articles based on independent cohorts were eligible for inclusion and articles citing these 7 were thoroughly searched (11 in total). Additionally, all medical records of our previously reported cohort were reviewed again to explore how the patients' background influenced diagnostic values of JA. RESULTS: We hypothesized that an oversimplified dichotomy of JA findings, pleocytosis, and meningitis created a misconception that JA is a universal indicator of meningitis. We clarify the difference between them and present altered mental status (AMS) as a key to decrease the sensitivity of JA. Notably, the sensitivity and specificity of JA were relatively low in unselected groups, while they tended to be high in the selected sub-groups with acute onset of headache and fever, without AMS or neurological deficits. Unselected populations included etiologies of pleocytosis other than acute meningitis, which might weaken the association between JA and pleocytosis. CONCLUSION: JA is not a universal, stand-alone, indicator of meningitis in febrile patients with headache. Therefore, we propose a stepwise approach for patients with suspected acute meningitis. AMS or neurological deficits suggest an intracranial pathology, which may necessitate a lumbar puncture. JA seems a useful tool for distinguishing acute aseptic meningitis from upper respiratory infection when used in the selected cohort of febrile patients (≥37°C) with recent-onset headache (within 2 weeks before presentation) and normal mental status. This approach and diagnostic values of JA should be further investigated by prospective studies using operationally sorted candidates.

Clinical pathologic case report: A 70-year-old man with inflammatory cerebral amyloid angiopathy causing headache, cognitive impairment, and aphasia.

A 70-year-old man presented with two months of worsening cognitive impairment, hallucinations, and difficulty speaking, with superimposed headaches. Cerebrospinal fluid analysis was notable for lymphocytic pleocytosis and elevated protein. Imaging studies revealed multiple acute and subacute infarcts with cortical microhemorrhages. The patient underwent a stereotactic brain biopsy. In this article, we discuss the patient's differential diagnosis, pathologic findings, ultimate diagnosis, and clinical outcome.

Impaired cerebrospinal fluid pressure.

Abnormalities of cerebrospinal fluid (CSF) pressure are relatively common and may lead to a variety of symptoms, with headache usually being the most prominent one. The clinical presentation of alterations in CSF pressure may vary significantly and show a striking similitude to several primary headache syndromes. While an increase in CSF pressure may be of primary or secondary origin, a pathologic decrease of CSF pressure is usually the result of a meningeal rupture with a resulting leakage of CSF. The pathophysiologic mechanisms of idiopathic intracranial hypertension (IIH) remain largely unknown. However recent evidence indicates that an abnormality in CSF outflow and absorption is likely to play a significant role. Treatment usually consists of a combination of weight loss and a pharmacologic approach using carbonic anhydrase inhibitors. Recent results of the first randomized, double-blind, placebo-controlled trial (RCT) with acetazolamide proved its efficacy in reducing headache and visual disturbances. Clinical evidence suggests efficacy for topiramate and furosemide but no RCT has been conducted to date to confirm these results. In contrast to IIH, spontaneous intracranial hypotension frequently remits spontaneously without specific treatment. If necessary, treatment options range from conservative methods to epidural blood or fibrin sealant patches and surgical interventions.

[Headhache secondary to intracranial hypotension in a Lumbar Spinal Stenosis Surgery].

Intracraneal hypotension headache is a well known syndrome in neurosurgery practice. In most cases cerebrospinal fluid leaks are caused by medical interventions, such as lumbar puncture, peridural anesthesia and surgical interventions on the spine. Clinical symptoms tipically show orthostatic headache that resolves in supine position, and other symptoms like neck tightness, vertigo and diplopia. RMI diagnostic confirms paquimeningeal enhancement and subdural hygromas. Conservative treatment usually includes bed resting, hydratation and administration of caffeine or glucocorticoids, resolving spontaneously in one to four months. The importance of the diagnosis lies in the differential diagnosis with other causes of headache, as symptomatic limiting factor in the rehabilitation of the patient and the same favorable prognosis.

[A HaNDL case with papilledema mimicking transient ischemic attack]. / Geçici iskemik atagi taklit eden ve papilödem saptanan bir HaNDL olgusu.

The syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL), is a rare, benign, self-limiting syndrome that is not well known. Cerebrospinal fluid examination (CSF) on clinical suspicion has diagnostic value for this syndrome, which has a rich neurological symptomatology that can mimic many diseases causing mortality and morbidity. Although the ethiopathogenesis of this syndrome is not fully known, autoimmunity is thought to be in the foreground. Described in this article is a HaNDL case that on first clinic presentation appeared to be a transient ischemic attack (TIA) with temporary but recurring neurological findings and normal CSF pressure accompanied by papilledema. Clinical features, epidemiology, ethiopathogenesis, differential diagnosis, and treatment of this syndrome are reviewed according to the literature.

Quantification and regulation of the adipokines resistin and progranulin in human cerebrospinal fluid.

BACKGROUND: Adipokines bearing the potential to cross the blood-brain barrier (BBB) are promising candidates for the endocrine regulation of central nervous processes and of a postulated fat-brain axis. Resistin and progranulin concentrations in paired serum and cerebrospinal fluid (CSF) samples of patients undergoing neurological evaluation and spinal puncture were investigated. MATERIALS AND METHODS: Samples of n = 270 consecutive patients with various neurological diseases were collected without prior selection. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay and serum and CSF routine parameters by standard procedures. Anthropometric data, medication and patient history were available. RESULTS: Serum levels of resistin and progranulin were positively correlated among each other, with respective CSF levels, low-density lipoprotein cholesterol levels and markers of systemic inflammation. CSF resistin concentrations were generally low. Progranulin CSF concentrations and CSF/serum progranulin ratio were significantly higher in patients with infectious diseases, with disturbed BBB function and with elevated CSF cell count and presence of oligoclonal bands. Both adipokines are able to cross the BBB depending on a differing patency that increases with increasing grade of barrier dysfunction. Whereas resistin represents a systemic marker of inflammation, CSF progranulin levels strongly depend on the underlying disease and dysfunction of blood-CSF barrier. CONCLUSIONS: Resistin and progranulin represent novel and putative regulators of the fat-brain axis by their ability to cross the BBB under physiological and pathophysiological conditions. The presented data provide insight into the characteristics of BBB function regarding progranulin and resistin and the basis for future establishment of normal values for CSF concentrations and CSF/serum ratios.

A retrospective review of sudden onset severe headache and subarachnoid haemorrhage on the clinical decision unit: looking for a needle in a haystack?

INTRODUCTION: Patients commonly present to the Emergency Department with sudden onset acute severe headache, but exclusion of significant secondary causes, particularly subarachnoid haemorrhage (SAH), is vital. The misdiagnosis of SAH is most likely in patients with a normal neurological examination, and the consequences can be disastrous. A noncontrast computed tomography (CT) brain scan is the initial investigation of choice, and most would recommend that, if negative, this be followed by a lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis. Many hospitals in the UK have developed Clinical Decision Unit (CDU) pathways to provide a standardized approach to the investigation and management of neurologically normal patients with headache suggestive of SAH. AIMS: The aims of this study were to describe the prevalence of SAH and to evaluate the performance of CT and LP in a CDU population with sudden onset acute severe headache. METHODS: A retrospective review of neurologically pristine patients admitted to a CDU pathway for exclusion of SAH was conducted. Structured case notes were reviewed; patient demographics, investigation results and clinical outcomes were recorded in each case. RESULTS: The overall prevalence of SAH in this population was 14/517 (2.7%). A noncontrast CT of the brain had a negative predictive value of 99.8%, reducing the post-test probability of having an angiogram-positive SAH detected by LP and CSF analysis to 0.21% (95% confidence interval 0.04-0.36%). CONCLUSION: The management of neurologically pristine patients with sudden onset severe headache on a CDU pathway is feasible. In light of the low prevalence of SAH in this population, the decision to follow a negative CT with an LP in all cases needs careful consideration, as CSF results may only rarely confer therapeutic benefit to patients suspected of SAH.