Elevated Cerebrospinal Fluid Protein Research Articles

Post-traumatic Meningitis: Risk Factors, Clinical Features, Bacteriology, and Outcome

Patients with post-traumatic meningitis (PTM) at two trauma centers from January 1992-December 1999 were retrospectively analyzed. Twenty-seven of 4,788 (0.56%) patients with head injury developed meningitis. Twenty-one (78%) patients were male. Mean age was 31.3 years. Twenty-three (85%) patients sustained blunt trauma and four (15%) had penetrating injuries. Median initial Glasgow coma scale (GCS) was 6. Twenty-one (78%) patients had pneumocephalus. Twelve (44%) patients had a cerebrospinal fluid (CSF) leak. Fever was seen in all patients and 23 (85%) displayed a decrease (greater than 2 points) in GCS. Twelve (44%) patients had an intracranial pressure (ICP) monitor, eight (30%) a ventriculostomy, and 12 (44%) underwent craniotomy prior to developing meningitis. Median interval between injury and diagnosis was 10 days. Pathogens were isolated from the CSF in 15 patients and brain tissue in one. Treatment in the remainder was based on elevated CSF white blood cell count, elevated CSF protein concentration, and low CSF glucose concentration. Measured functional outcome was good in 10 (37%) patients while 8 (30%) had a residual disability requiring dependent care and 5 (19%) remained in a vegetative state. Four (15%) patients died. Admission GCS was predictive of a good functional outcome (p < 0.01), but did not predict death from infection.

Fulminant acute disseminated encephalomyelitis mimicking acute bacterial menigoencephalitis

Most patients with acute disseminated encephalomyelitis (ADEM) recover quickly under corticosteroid treatment and have a favourable long-term prognosis. We report on a young woman with acute onset of an extensive and solitary white-matter lesion in the left hemisphere. Fever, high pleocytosis and elevated protein in cerebrospinal fluid initially suggested bacterial meningoencephalitis. The patient died from brain herniation despite maximal conservative therapy. Histological changes in necropsy were consistent with the diagnosis ADEM. Treatment options of fulminant ADEM are discussed.

Polyradiculonévrite aiguë inflammatoire révélant une neuropathie héréditaire avec hypersensibilité à la pression

Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant peripheral neuropathy characterized by compressive focal neuropathies and an underlying sensorimotor demyelinative polyneuropathy. It is usually caused by a 1.5 Mb deletion of the PMP22 gene (17p11.2). We describe the case of a 31 year-old woman who presented with acute demyelinative peripheral polyneuropathy affecting the four limbs and elevated cerebrospinal fluid protein content a few days after a viral illness. Acute inflammatory demyelinating polyneuropathy (AIDP, Guillain-Barré syndrome) was suspected. However, electrophysiologic examination suggested HNPP and subsequent genetic testing was confirmatory. This case demonstrates that HNPP can present in an acute manner, mimicking AIDP.

Diagnosis, Treatment, and Prognosis of Mycoplasma pneumoniae Childhood Encephalitis: Systematic Review of 58 Cases

Most of the knowledge on Mycoplasma pneumoniae encephalitis in children is based on case reports or small case series. The aim of this study was to assess the important features of the disease by a systematic review of previously published cases. Overall, 58 cases (22 female, 36 male; median age 10 years, range: 2-17 years), derived from 38 reports, were reviewed. Forty-five patients (76%) had flulike or respiratory symptoms prior to the onset of neurologic disease, and 23 patients (40%) presented with pulmonary infiltrates. Cerebrospinal fluid (CSF) pleocytosis (mostly mononuclear cells) and elevated cerebrospinal fluid protein counts were present in 34 (59%) and 21 (36%) patients, respectively. Cranial computed tomography (CT) or magnetic resonance imaging (MRI) abnormalities were seen in 18 (31%) and 17 (29%) patients, respectively, whereby various different presentations were observed. Forty-four patients (76%) received antimicrobial therapy active against mycoplasmas, most frequently erythromycin (n = 29) or minocycline (n = 6). Only in one patient, cure was directly attributed to antimicrobial therapy (with chloramphenicol) by the respective authors. Thirty-three patients (57%) recovered without sequelae, 20 patients (34%) had minor to major sequelae, and 5 patients (9%) died. A high cerebrospinal fluid cell count, cerebrospinal fluid protein elevation, and higher age were associated with an unfavorable outcome.

Correlation of cerebrospinal fluid (CSF) cell counts and elevated CSF protein levels with enterovirus reverse transcription-PCR results in pediatric and adult patients.

During the 2001, 2002, and 2003 enterovirus seasons, we investigated the correlations between cerebrospinal fluid (CSF) nucleated cell counts and elevated CSF protein levels and the detection of enteroviral RNA by reverse transcription (RT)-PCR. Our objective was to determine if pleocytosis and/or elevated protein levels were predictive of positive RT-PCR results for enterovirus. We were also interested in determining if the presence of West Nile virus during the 2002 enteroviral season contributed to a change in these correlations. We found that in the group of patients aged >2 months, the absence of pleocytosis was highly predictive of a negative RT-PCR result. Elevated CSF protein level was not a good predictor of RT-PCR positivity for enterovirus and did not add to the diagnostic sensitivity or specificity of pleocytosis.

The management of Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is a rare cause of severe polyneuropathy in children. We now recognise that GBS is made up of distinct subtypes, with different clinical, electrodiagnostic and pathological findings. The diagnosis of GBS is based on the classical triad of weakness, areflexia and elevated cerebrospinal fluid (CSF) protein without pleocytosis. Early recognition and effective treatment of GBS may reduce morbidity and mortality. The management of GBS includes acute treatment of the paralysis and associated complications, the treatment of the underlying cause, and the long-term rehabilitation of the patient. This article aims to provide a clear evidence-linked care pathway for the management of GBS from the time of presentation to rehabilitation.

Modern management of children with haemophagocytic lymphohistiocytosis.

Modern management of children with haemophagocytic lymphohistiocytosis.

Sarcoidosis of the anterior visual pathway: 24 new cases.

To describe the clinical spectrum and a rational approach to the diagnosis of anterior visual pathway sarcoidosis. Retrospective chart review of all patients examined in neuro-ophthalmic consultation by 1 author from 1989 to 1998 with a diagnosis of sarcoidosis. There were 24 patients (17 female, 7 male, mean age 40 years) with anterior visual pathway sarcoidosis, 17 (71%) of whom were not previously known to have sarcoidosis. Visual acuity ranged from 20/20 to NLP. Normal fundi were observed in 15%. Among the 85% who had fundus abnormalities, pallor was present in 55%, disc edema in 26%, periphlebitis/sheathing in 14%, and optic disc granuloma in 10%. Ten patients (42%) had uveitis, active in only 3 (13%). An elevated angiotensin-converting enzyme (ACE) was present in 16 (76%) of 21 patients tested; evidence of sarcoidosis on chest radiograph was present in 13 (72%) of 18; gallium scanning was abnormal in 13 (93%) of 14; neuroimaging abnormalities of the optic nerves, chiasm, or tract were present in 16 (70%) of 23; lymphocytic pleocytosis or elevated cerebrospinal fluid protein was identified in 14 (88%) of 16 patients, with both values elevated in 7 (44%) patients. Histologic confirmation was obtained in 13 (81%) of 16 who underwent biopsy; in the remaining patients, diagnosis was based entirely on clinical and laboratory evidence. Anterior visual pathway disease may be underrecognized as a presentation of sarcoidosis. Classic fundus findings of periphlebitis and optic granuloma are typically absent. An aggressive diagnostic evaluation may help establish the diagnosis early in its course.

New Pattern of Brain MRI Lesions in Isolated Complex I Deficiency

We describe a boy presenting at the end of the first year of life with severely delayed motor development and only mild mental retardation. Neurological examination revealed axial hypotonia, mild ataxia and pyramidal signs. Elevated lactate and protein in cerebrospinal fluid were the most prominent laboratory abnormalities. Brain MRI showed severe supratentorial white matter changes. Cerebellar white matter appeared normal whereas the signal of the atrophic cerebellar cortex was markedly increased. In vivo 1H-magnetic resonance spectroscopy of the parietooccipital white matter region showed a distinct resonance of lactate. By means of biochemical analysis of respiratory chain enzymes in fibroblasts, the diagnosis of an isolated complex I deficiency could be established in our patient.

MANAGEMENT OF INFLAMMATORY NEUROPATHIES

Inflammatory neuropathies are uncommon but important to diagnose because they are treatable. This review summarises the clinical approach to diagnosis and treatment of Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy...

Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA.

Laboratory findings for cerebrospinal fluid (CSF) specimens were correlated with clinical presentations and histories in 55 cases of encephalitis or meningitis due to herpes simplex virus (HSV), as determined by polymerase chain reaction (PCR)-based detection of HSV DNA. Sixteen patients (29%) had HSV encephalitis (HSVE), 3 had mild or "atypical" meningoencephalitis, 34 (64%) had HSV meningitis (HSVM), and 1 had disseminated neonatal HSV infection. CSF findings included elevated leukocyte counts and/or elevated CSF protein levels in all HIV DNA-positive specimens. CSF leukocyte and protein abnormalities were more pronounced in cases of HSVM than they are in cases of HSVE. Patients with HSVE who had only mild CSF abnormalities also had minimal numbers of erythrocytes in the CSF. Patients with HSVM were younger than were patients with HSVE and were predominantly female. Eleven patients with HSVM reported having prior episodes, and 5 reported a history of recurrent headaches. These findings suggest that milder forms of HSV infection of the central nervous system may be identified by PCR for HSV. Prescreening of CSF specimens for the presence of leukocytes or elevated protein level may improve test utilization.

88th ENMC International Workshop: Childhood chronic inflammatory demyelinating polyneuropathy (including revised diagnostic criteria), Naarden, The Netherlands, December 8–10, 2000

88th ENMC International Workshop: Childhood chronic inflammatory demyelinating polyneuropathy (including revised diagnostic criteria), Naarden, The Netherlands, December 8–10, 2000

Degenerative Disorders of the Central Nervous System

Degenerative Disorders of the Central Nervous System

Guillain-Barre syndrome and Campylobacter jejuni infection

Guillain-Barre syndrome (GBS) is the most common cause of acute neuromuscular paralysis, usually due to acute inflammatory demyelinating polyradiculoneuropathy. The presence of activated T lymphocytes and antibodies against peripheral nerve myelin suggests an autoimmune pathogenesis, although there is wide heterogeneity. Gangliosides are sialylated glycolipids widely distributed in nervous system membranes. GBS is usually preceded by an infection, most frequently Campylobacter jejuni enteritis, but also cytomegalovirus, Mycoplasma pneumoniae or Epstein-Barr virus. Patients with GBS and C. jejuni infection are more likely to have neurophysiological features of axonal neuropathy, antibodies to ganglioside GM1, pure motor GBS, a less elevated CSF protein concentration and a worse outcome than other GBS patients. Although molecular mimicry between peripheral nerve gangliosides and epitopes present on C. jejuni lipopolysaccharide could explain some of these associations, this hypothesis is inadequate to account for many aspects of the pathogenesis of GBS.

Acute Sensory Neuropathy

A 62-year-old man presented with an acute onset of symmetric upper and lower extremity paresthesias. Neurological examination showed normal motor strength throughout with areflexia and reduced vibratory and proprioceptive sense in all four extremities. A lumbar puncture performed 6 weeks after onset demonstrated elevated cerebrospinal fluid protein with no cells. Electrodiagnostic testing 7 weeks after onset revealed a primarily sensory neuropathy with normal motor conduction and needle electromyographic studies Symptoms stabilized within 3 weeks of onset and improvement began within 2 months. Except for the absence of motor disturbance, this case appears to resemble Guillain-Barré syndrome.

New concepts of Guillain-Barré syndrome.

Guillain-Barré syndrome is an acute autoimmune polyradiculoneuropathy with a clinical presentation of flaccid paralysis with areflexia, variable sensory disturbance, and elevated cerebrospinal fluid protein without pleocytosis. Although Guillain-Barré syndrome previously had been viewed as a unitary disorder with variations, it currently is viewed as a group of syndromes with several distinctive subtypes. These include the principal subtype prevalent in the Western world (acute inflammatory demyelinating polyradiculoneuropathy, and others, each with distinctive electrodiagnostic and pathologic features, including acute motor axonal neuropathy), acute motor-sensory axonal neuropathy, Miller Fisher syndrome, and perhaps others. The clinical and pathologic features of these Guillain-Barré syndrome subtypes are reviewed, and the role of antecedent infections, particularly Campylobacter jejuni gastroenteritis, and the role of antiganglioside antibody responses are reviewed with respect to pathogenesis. Treatment of Guillain-Barré syndrome includes both important supportive measures and immunotherapies, specifically high-dose intravenous immunoglobulin and plasma exchange.

Chronic Inflammatory Demyelinating Polyneuropathy Presenting With Headache and Papilledema

Chronic inflammatory demyelinating polyneuropathy is a disorder typified clinically by motor and sensory neuropathy of at least 2 months' duration and pathologically by multifocal inflammatory demyelination. Its usual presentation is with features reflecting the polyneuropathy, namely limb weakness with hyporeflexia or areflexia and sensory symptoms of glove and stocking distribution. In this report, we detail the course of a 53-year-old man who presented to our neurological service with a severe headache in association with papilledema. The initial diagnosis considered was of possible primary intracranial pathology. Two months later, he developed limb weakness and sensory symptoms typical of chronic inflammatory demyelinating polyneuropathy. His headache, papilledema, and limb symptoms responded to oral corticosteroid therapy, the standard treatment for this type of neuropathy. We hypothesize that his headache and papilledema were due to the elevated cerebrospinal fluid protein level as a result of the polyneuropathy. To our knowledge, this is the first report of headache being a prominent and early symptom of this disorder.

Profound cerebrospinal fluid pleocytosis and Froin's Syndrome secondary to widespread necrotizing vasculitis in an HIV-positive patient with varicella zoster virus encephalomyelitis

Demonstration of the direct involvement of cranial blood vessels by varicella zoster virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalomyelitis (VZVE) is still, however, debated. Most VZVE patients are immunocompromised and show little inflammation, either pre-mortem in cerebrospinal fluid (CSF) or at autopsy. We describe an HIV-positive patient with a moderately depressed CD4 count (304) who presented with massively elevated CSF protein (1800 mg/dl), bloody CSF and pleocytosis (1300 white blood cells (WBC)/mm3). His CSF was positive for VZV DNA by PCR. He was treated with acyclovir and foscarnet, but died. At autopsy, an unusually widespread, inflammatory, transmural vasculitis caused by VZV affected meningeal vessels at virtually all brain stem and spinal cord levels, causing multiple subpial hemorrhages and necrosis. Virus DNA in multiple areas of brain, brainstem and spinal cord was readily revealed by PCR, but not by the presence of viral inclusions, IHC or ISH. This case, with a clinically confusing presentation for VZVE, illustrates the extensive, albeit infrequent, degree of necrotizing vasculitis and CSF abnormalities that VZV is capable of producing. Antiviral therapy may have inhibited VZV genome replication and subsequent antigen production, resulting in negative ISH and IHC studies, but generated increased VZV genomic fragments that were detectable by the more sensitive PCR technique.

Cerebrospinal fluid profile in patients with acute Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood for which there is currently no diagnostic test. The clinical presentation of KD may initially resemble other infectious diseases, including bacterial or viral meningitis. For this reason lumbar puncture (LP) is sometimes performed during the evaluation of these patients. To understand the range of cerebrospinal fluid (CSF) changes that may be associated with acute KD, a retrospective review of unselected KD patients from three pediatric centers was performed. Retrospective chart review was performed on KD patients evaluated during the first 10 days of illness who had an LP performed before the administration of intravenous gamma-globulin. During the 6.5-year study period, 46 KD patients underwent LP as part of their clinical evaluation. Of these patients 18 (39.1%) had CSF pleocytosis, 1 (2.2%) had a CSF glucose <45 mg/dl and 8 (17.4%) had an elevated CSF protein. Of the patients with CSF pleocytosis, the median white blood cell count was 22.5 cells (range, 7 to 320 cells), with a median of 6.0% neutrophils (range, 0 to 79%) and 91.5% mononuclear cells (range, 11 to 100%). In the present series approximately one-third of KD patients who underwent an LP had CSF pleocytosis with a mononuclear cell predominance. No patient had significant hypoglycorrhachia, and elevation of the CSF protein was uncommon. CSF abnormalities were similar between US and Japanese KD patients. The basis for the CSF pleocytosis in acute KD patients remains unknown.

Inflammatory Demyelinating Neuropathy in Patients with End-Stage Renal Disease Receiving Continuous Ambulatory Peritoneal Dialysis (Capd)

To report on 3 patients with inflammatory demyelinating peripheral neuropathy in strong temporal coincidence with the initiation of peritoneal dialysis (PD) therapy. Nephrology and Neurology Department of the University Hospital, Munich, Germany. Three patients with end-stage renal failure presented with the clinical picture of inflammatory demyelinating peripheral neuropathy within 4 to 10 weeks after start of continuous ambulatory peritoneal dialysis (CAPD). They had acute or subacute onset of lower extremity or generalized weakness, diminished reflexes, elevated spinal fluid protein levels, and signs of demyelinating neuropathy on electrophysiological testing. Clinical follow-up, nerve conduction studies, cerebral spinal fluid (CSF). All patients did not improve under intensified PD therapy but took profit from immunomodulatory therapy. One bed-bound patient improved after change to hemodialysis and showed complete remission after renal transplantation. Because of strong temporal coincidence, a causal relationship between CAPD and inflammatory demyelinating peripheral neuropathies can be suspected in these 3 patients.