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.

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.

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.

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 combined spinal-epidural technique for labor analgesia and symptomatic relief in two parturients with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension is a condition consisting of increased intracranial pressure of unknown etiology, predominantly affecting obese women of childbearing age. Symptomatic relief can be provided by lumbar puncture and withdrawal of cerebrospinal fluid, and the technique has been described in laboring women using an intrathecal catheter. We present two patients who achieved both labor analgesia and symptomatic relief via a combined spinal-epidural technique with small volume cerebrospinal fluid withdrawal. Both women complained of headache of at least a 5 on a 10-point pain scale at the time of labor induction. Between 5 and 6 mL of cerebrospinal fluid were withdrawn at the time of combined spinal-epidural insertion and pain relief was successfully achieved with patient-controlled epidural anesthesia. One patient proceeded to cesarean delivery for fetal indications under epidural anesthesia. Both women described significant improvement in headache symptoms that persisted until discharge from hospital, and neither developed new neurologic symptoms. A combined spinal-epidural technique with a small volume of cerebrospinal fluid withdrawal may provide labor analgesia and symptomatic relief in the parturient with idiopathic intracranial hypertension.

Abnormal pressure waves in headache sufferers with bilateral transverse sinus stenosis.

INTRODUCTION: Bilateral transverse sinus stenosis (BTSS) has been reported to be associated with idiopathic intracranial hypertension without papilloedema in headache sufferers. SUBJECTS AND METHODS: To test the accuracy of short-term cerebrospinal fluid (CSF) pressure monitoring through a lumbar needle for detection of elevated intracranial pressure in headache sufferers with BTSS, we prospectively performed lumbar puncture in order to measure lumbar CSF opening pressures and to monitor, for 1 h, the CSF pressure in 48 consecutive headache sufferers with BTSS and in 50 consecutive headache sufferers with normal appearance of transverse sinuses or stenosis of one transverse sinus. RESULTS: Of the 48 headache sufferers with BTSS, 18 (37.5%) had elevated CSF opening pressure and abnormal pressure waveforms, but short-term CSF pressure monitoring revealed abnormal pressure waves associated with elevated mean CSF pressure also in 26 (86.6%) out of 30 patients who had normal opening pressures. None of the 50 headache sufferers with normal appearance of transverse sinuses or stenosis of one transverse sinus had abnormal pressure waves and elevated CSF pressures. CONCLUSIONS: In this study, short-term CSF pressure monitoring through a lumbar needle revealed abnormal pressure waves and elevated mean CSF pressures in the majority of headache sufferers with BTSS who had normal CSF opening pressures. These findings demonstrate the accuracy of short-term CSF pressure monitoring through a lumbar needle in estimating CSF pressure; they also highlight that a single-spot opening pressure measurement has a low accuracy for recognition of increased intracranial pressure in headache sufferers with BTSS.

Primary central nervous system vasculitis and moyamoya disease: similarities and differences.

Primary central nervous system vasculitis (PCNSV) and moyamoya disease (MMD) represent rare and poorly-understood causes of stroke. Both may present with similar clinical and auxiliary findings, but differentiation is extremely important because they require different treatment regimens. Our cohort included 21 white patients with PCNSV and 21 white patients with MMD. Clinical and diagnostic features were obtained by retrospective chart review; follow-up information and outcome were obtained prospectively. Data were compared between patients with PCNSV and MMD using Chi square test or Fisher's exact test for categorical data and Mann-Whitney U test for continuous data. The mean age at symptom onset was 42.48 years in PCNSV and 31.0 years in MMD (p = 0.008). All patients with MMD presented with ischemic events while cerebral ischemia was observed in only 14 of 21 patients (66.7%) with PCNSV (p = 0.004). There was no significant difference regarding the frequency of headaches, which represented an important symptom in both conditions. Conventional cerebral angiography verified correct diagnosis in 13 of 17 patients (76.5%) with PCNSV while angiogram verified correct diagnosis in all patients with MMD (p = 0.032). MRI and cerebrospinal fluid studies were appropriate to differentiate between the inflammatory and the non-inflammatory disease. Three PCNSV patients and two MMD patients died within documented follow-up. Despite important pathophysiological and angiographic differences, PCNSV and MMD may present with similar clinical and auxiliary findings. An intensive workup including MRI, conventional cerebral angiography and CSF studies is required to avoid misdiagnosis.

CSF levels of cytokines in neuro-Behçet's disease.

BACKGROUND: Neurological manifestations of Behçet's disease (neuro-Behçet's disease) present in 5-30% of patients. Although cytokines play a pivotal role in pathogenesis of Behçet's disease, published studies about the cerebrospinal fluid (CSF) levels of cytokines in neuro-Behçet's disease are scanty. METHODS: Nine patients with active parenchymal, one patient with non-parenchymal neuro-Behçet's disease, six patients with headache attributed to Behçet's disease, 13 patients with viral meningitis, and 19 healthy controls were recruited. Interleukin 6, 8, 10, tumor necrotic factor-alpha, and interferon-gamma were measured in the CSF using enzyme-linked immunosorbent assay method. RESULTS: Patients with viral meningitis had significantly higher levels of all investigated cytokines except for interferon-gamma in comparison with the patients with parenchymal neuro-Behçet's disease, headache attributed to Behçet's disease and controls (P values <0.05). CSF interleukin 6 was significantly higher in patients with parenchymal neuro-Behçet's disease in comparison with the controls (P=0.025). CSF levels of investigated cytokines had no significant difference between patients with headache attributed to Behçet's disease and controls (P values >0.05). Patients with headache attributed to BD and patients with parenchymal NBD had no significant difference in measured cytokines (P values >0.05). CONCLUSION: In contrast to some previous studies, our investigation showed loss of analogy between CSF cytokine profiles of patients with parenchymal neuro-Behçet's disease and viral meningitis. Also we postulated a crucial role for interleukin 6 in immunopathogenesis of neuro-Behçet's disease.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

OBJECTIVE: To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. BACKGROUND: NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. METHODS: CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). RESULTS: CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. CONCLUSION: An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

Headache in cerebrospinal fluid volume depletion syndrome: a case report.

Cerebrospinal fluid (CSF) volume depletion syndrome is due to leakage of cerebrospinal fluid through lesions of the dural sac at the level of the cranial base or of the spine. When past medical history is negative for recent trauma or surgery, the term spontaneous intracranial hypotension (SIH) is used. SIH is characterized clinically by orthostatic headache, neck pain, nausea, emesis, horizontal diplopia, tinnitus, plugged ear, hearing difficulties, blurring of vision, facial numbness, and upper limb radicular symptoms. In SIH, brain and cervical MR scans show a diffuse pachymeningeal gadolinium enhancement that ends at the site of CSF leakage. The application of epidural blood patches has been proposed as an effective therapy for SIH. Here we describe a case of SIH with very unusual headache features; the patient reported a paradoxical pattern of postural headache provoked by clinostatic position. The CSF leakage was identified at the convexity of the skull and headache disappeared following treatment with fluid, analgesics and steroids.

The role of the biochemistry department in the diagnosis of pituitary apoplexy.

A 47-year-old man presented with severe clinical hypoglycaemia. He had long-standing insulin-dependent diabetes with previously good glycaemic control. Intense headaches and vomiting initiated hospitalization. A brain computed tomography (CT) scan was normal, and a lumbar puncture showed elevated cerebrospinal fluid (CSF) protein [0.67 g/L; normal range (NR) 0.15-0.45 g/L], suggesting resolving viral meningitis. Routine thyroid function tests were abnormal (free thyroxine 10.6 pmol/L, NR 9-22.5 pmol/L; thyroid-stimulating hormone 0.16 mU/L, NR 0.35-5 mU/L). In the absence of evident thyroid therapy, the laboratory policy required an urgent cortisol assay to be added; this was very abnormal (42 nmol/L), suggesting hypopituitarism. Later analysis showed that concentrations of gonadotrophins and adrenocorticotrophin were low. An urgent pituitary magnetic resonance imaging scan revealed an unsuspected pituitary tumour with recent haemorrhage (pituitary apoplexy). The patient was given intravenous hydrocortisone and then stabilized on oral hydrocortisone, thyroxine and mesterolone. He made a full recovery and the hypoglycaemia resolved. The normal brain CT scan was falsely reassuring and the CSF protein was not due to viral meningitis but to haemorrhage into the pituitary tumour. If laboratory policy had not required the urgent cortisol assay be added, the diagnosis of hypopituitarism would have been delayed or even missed altogether. This could have led to the death of the patient.