Intrathecal BCR transcriptome in multiple sclerosis versus other neuroinflammation: Equally diverse and compartmentalized, but more mutated, biased and overlapping with the proteome.

The mechanisms driving the intrathecal synthesis of IgG in multiple sclerosis (MS) are unknown. We combined high-throughput sequencing of transcribed immunoglobulin heavy-chain variable (IGHV) genes and mass spectrometry to chart the diversity and compartmentalization of IgG-producing B cells in the cerebrospinal fluid (CSF) of MS patients and controls with other neuroinflammatory diseases. In both groups, a few clones dominated the intrathecal IGHV transcriptome. In most MS patients and some controls, dominant transcripts matched the CSF IgG. The IGHV transcripts in CSF of MS patients frequently carried IGHV4 genes and had more replacement mutations compared to controls. In both groups, dominant IGHV transcripts were identified within clusters of clonally related B cells that had identical or related IGHV transcripts in the blood. These findings suggest more pronounced affinity maturation, but an equal degree of diversity and compartmentalization of the intrathecal B-cell response in MS compared to other neuroinflammatory diseases.

[Acute transverse myelitis and Lyme borreliosis: a case report]. / Myélite transverse aiguë et maladie de Lyme: à propos d'un cas.

Lyme disease is an infectious disease caused by a spirochete of the Borrelia sensu lato group. Its incidence has greatly increased in recent years. The main vector is a tick of the Ixodes family. Clinical manifestations are multiple and show the multi-organ character of the disease. In terms of frequency, joint and neurological presentations, respectively more frequent in North America and Europe, are the main manifestations after cutaneous symptoms, of which erythema migrans is the most common, followed by cardiac and ocular signs. Other signs exist but are anecdotal. Neuroborreliosis manifests itself most often with peripheral facial palsy, but there are other clinical forms, which include acute myelitis (4-5% of neuroborreliosis). We present here the case of a 16-year-old teenager with acute myelitis and meningeal involvement due to Lyme disease, who presented with atypical symptoms (massive and rapid weight loss, vomiting). MRI showed localized marrow edema as well as leptomeningeal and root enhancement. Lumbar puncture showed lymphocytic pleocytosis. Lyme serology was positive both in blood and cerebrospinal fluid. Even if acute myelitis remains exceptional among neuroborreliosis manifestations, this diagnosis has to be thought of when a child presents with unexplained neurological symptoms.

Diabetic cervical radiculoplexus neuropathy: a distinct syndrome expanding the spectrum of diabetic radiculoplexus neuropathies.

Diabetic lumbosacral radiculoplexus neuropathy is a subacute painful, asymmetrical lower limb neuropathy due to ischaemic injury and microvasculitis. The occurrence of a cervical diabetic radiculoplexus neuropathy has been postulated. Our objective was to characterize the clinical features and pathological alterations of diabetic cervical radiculoplexus neuropathy, to see if they are similar to diabetic lumbosacral radiculoplexus neuropathy and due to ischaemic injury and microvasculitis. We identified patients with diabetic cervical radiculoplexus neuropathy by review of the Mayo Clinic database from 1996 to 2008. We systematically reviewed the clinical features, laboratory studies, neurophysiological findings, neuroimaging and pathological features and compared the findings with a previously published diabetic lumbosacral radiculoplexus neuropathy cohort. Eighty-five patients (56 males, 67 with Type 2 diabetes mellitus) were identified. The median age was 62 years (range 32-83). The main presenting symptom was pain (53/85). At evaluation, weakness was the most common symptom (84/85), followed by pain (69/85) and numbness (56/85). Neuropathic deficits were moderate (median motor neuropathy impairment score 10.0 points) and improved at follow-up. Upper, middle and lower brachial plexus segments were involved equally and pan-plexopathy was not unusual (25/85). Over half of patients (44/85) had at least one additional body region affected (30 contralateral cervical, 20 lumbosacral and 16 thoracic) as is found in diabetic lumbosacral radiculoplexus neuropathy. Recurrent disease occurred in 18/85. Neurophysiology showed axonal neuropathy (80/80) with paraspinal denervation (21/65), and abnormal autonomic (23/24) and sensory testing (10/13). Cerebrospinal fluid protein was elevated (median 70 mg/dl). Magnetic resonance imaging showed brachial plexus abnormality in all (38/38). Nerve biopsies (11 upper and 11 lower limbs) showed ischaemic injury (axonal degeneration, multifocal fibre loss 15/22, focal perineurial thickening 16/22, injury neuroma 5/22) and increased inflammation (epineural perivascular inflammation 22/22, haemosiderin deposition 6/22, vessel wall inflammation 14/22 and microvasculitis 5/22). We therefore conclude that (i) diabetic cervical radiculoplexus neuropathy is a predominantly monophasic, upper limb diabetic neuropathy with pain followed by weakness and involves motor, sensory and autonomic fibres; (ii) the neuropathy begins focally and often evolves into a multifocal or bilateral condition; (iii) the pathology of diabetic cervical radiculoplexus neuropathy demonstrates ischaemic injury often from microvasculitis; and (iv) diabetic cervical radiculoplexus neuropathy shares many of the clinical and pathological features of diabetic lumbosacral radiculoplexus neuropathy, providing evidence that these conditions are best categorized together within the spectrum of diabetic radiculoplexus neuropathies.

Cauda equina syndrome in ankylosing spondylitis: successful treatment with lumboperitoneal shunting.

STUDY DESIGN: Retrospective study. OBJECTIVE: To assess outcomes after lumboperitoneal shunting for CES with dural sac dilation and multiple arachnoid diverticula in patients with long-standing AS. SUMMARY OF BACKGROUND DATA: Cauda equina syndrome (CES) is a rare complication of long-standing ankylosing spondylitis (AS). Neurologic symptoms occur insidiously and have a poor prognosis without effective treatment. METHODS: We retrospectively studied cases seen between 1997 and 2009 at our university-hospital rheumatology department. RESULTS: We identified 9 patients with AS and dural sac dilation (mean age: 64, range: 38-75), of whom 8 experienced CES 29.1 years on average (range: 10-51) after AS onset. Presenting symptoms were urinary abnormalities (n = 4), sensory abnormalities (n = 6), or radicular or low back pain (n = 4). The symptoms worsened progressively, with mild (n = 3) to severe (n = 1) motor deficiency, sphincter dysfunction (urinary [n = 6] and/or anal [n = 4] sphincter), and impotence (n = 3). Magnetic resonance imaging showed dural sac dilation (n = 9), multiple lumbar arachnoid diverticula (n = 6), erosions of the laminae and spinous processes (n = 6), and nerve-root tethering (n = 6) with adhesion to the dura mater and vertebrae (n = 7). Cerebrospinal fluid (CSF) flow study by magnetic resonance imaging was performed in 2 patients and showed communication of the diverticula with the CSF. Lumboperitoneal shunting, performed in 5 patients, was followed by improvements in sensation (n = 4), urinary symptoms (n = 2), anal continence (n = 3), and pain. Full recovery of muscle strength was noted in 3 patients. Improvements persisted after a mean of 49 months (range: 18-96). CONCLUSION: Lumboperitoneal shunting induced substantial improvements in all 5 patients treated with this procedure. This result suggests that AS-related CES may be due to chronic arachnoiditis and dural fibrosis leading to diminished CSF resorption with dural sac dilation and diverticula formation.

[Acute polyradiculitis--from prickling to intensive care]. / Akuutti polyradikuliitti--"tikkuilusta" tehohoitoon.

Characteristic symptoms of acute polyradiculitis are parestesia beginning from the feet and a symmetrically ascending myasthenia. The symptomatology, which may vary from mild asthenia to complete tetraplegia, may be accompanied by asphyxia and symptoms of the autonomic nervous system and cranial nerves. Polyradiculitis is often preceded by an infection. An elevated protein level of the cerebrospinal fluid without cellular reaction is the typical finding, but a specific laboratory test is not available. The clinical course is monophasic and relapses are uncommon. The natural prognosis for recovery is fairly good, but one fifth are left with functional impairment and the disease may even be fatal.

Cauda equina syndrome due to leptomeningeal carcinomatosis of the ovary.

BACKGROUND: Serous cystadenocarcinoma is the most common malignant ovarian tumor. 85% are associated with extraovarian spread at the time of diagnosis. Cauda equina syndrome due to leptomeningeal ovarian serous cystadenocarcinomatosis is rare. CASE: A 66-year-old female with stage IV ovarian papillary serous cystadenocarcinoma presented with perianal numbness and sphincter dysfunction. On exam she had decreased anal tone with saddle anesthesia. Her MRI did not demonstrate any leptomeningeal involvement. CSF showed malignant cells consistent with metastatic ovarian adenocarcinoma. She received intrathecal methotrexate, capecitabine and bevacizumab. She expired 8 months later. CONCLUSION: Ovarian cancer metastasizng to the cauda equina should be highly suspected based on the clinical presentation alone, even with unremarkable imaging studies. CSF cytology should be checked in cases presenting with cauda equina syndrome.

Cauda equina and conus medullaris syndrome in sarcoidosis.

BACKGROUND: Neurosarcoidosis is a rare manifestation of sarcoidosis. Involvement of the nervous system in sarcoidosis can range from peripheral or cranial neuropathy to central nervous system disease. Cauda equina sarcoidosis is distinctly rare. REVIEW SUMMARY: The authors present a 58-year-old patient with systemic sarcoidosis who developed cauda equina and conus medullaris syndrome. Seventeen previous published cases of cauda equina sarcoidosis are reviewed. The history of systemic sarcoidosis, cerebrospinal fluid characteristics of lymphocytic pleocytosis with elevated protein, and evidence of acute denervation by needle electromyography are helpful in the diagnosis of this condition. Early diagnosis and treatment of cauda equina sarcoidosis usually provide a rapid recovery and yield a good prognosis. CONCLUSION: Although rare, sarcoidosis should be considered in the differential diagnosis of cauda equina syndrome, particularly in patients with unclear etiology.

[Neurologic complications of varicella in adults]. / Les complications neurologiques de la varicelle chez l'adulte.

Three patients aged 32, 30 and 36 years, had chicken pox then developed acute cerebellar ataxia (for two) and acute polyradiculoneuritis. Cerebrospinal fluid (CSF) protein content was increased and varicella virus serology was positive in both blood and CSF. All three patients improved with aciclovir.

Acute inflammatory demyelinating polyradiculopathy in children: clinical and electrodiagnostic studies.

Clinical and electrophysiological features in 43 children with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were retrospectively studied. More than one-third of these children were less than 3 years old. Some distinctive clinical features specific to adults or to children were identified. Initial symptoms such as ataxia and severe limb or back pain were more frequent in children. By using the criteria suggested here, according to our neurophysiological findings, the diagnosis of AIDP could be proposed as early of the first days of illness in 90% of the children and is confirmed during the second week. The neurophysiological evolution was very similar in children and adults except that recovery occurred sooner in children. Prognosis was better in childhood (complete recovery in all but 2 patients with minor disabilities).

Encephalomyeloradiculopathy associated with Epstein-Barr virus: primary infection or reactivation?

INTRODUCTION: Encephalomyeloradiculopathy (EMR) is a new syndrome, characterized by extensive involvement of the nervous system at different levels, including brain, medulla and spinal roots. We describe a patient presenting with prodromal febrile illness, followed by a wide infection of the nervous system with transverse myelitis and less severe meningitis, encephalitis and polyradiculopathy. The patient was treated with high-dose corticosteroids, antibiotics and acyclovir; in spite of therapy his condition improved very slowly, with severe neurological sequelae. MATERIAL AND METHODS: Antiviral antibodies were searched for in serum and cerebrospinal fluid (CSF) by commercially available ELISA kits. Viral investigations were performed by cell culture isolation and search for viral antigens, and genomic nucleic acids were investigated by polymerase chain reaction (PCR). RESULTS: Virological and serological studies evidenced a primary infection by cytomegalovirus (CMV), possibly responsible for the prodromal illness, persisting in the course of the disease. PCR performed in the peripheral blood mononuclear cells (PBMCs), DNA collected early and in the CSF drawn 30 days after the onset of the disease showed Epstein-Barr virus (EBV) DNA. The serum panel of EBV antibodies was typical of an intercurrent virus reactivation, more than of a primary infection. CONCLUSION: EBV is known to be highly infectious for the nervous system, in this case of EMR the presence of DNA sequences in the PBMCs and CSF suggests that EBV plays a role in the development of this newly described syndrome.

Acute lumbosacral polyradiculopathy due to cytomegalovirus in advanced HIV disease: CSF findings in 17 patients.

OBJECTIVES: To describe the abnormalities in CSF from HIV infected patients with acute lumbosacral polyradiculopathy (ALP) caused by cytomegalovirus (CMV) infection. METHODS: Retrospective case notes and laboratory records were reviewed for 17 consecutive patients with CMV associated ALP admitted to specialist HIV/AIDS units at UCL Hospitals and Chelsea and Westminster Hospital. RESULTS: Infection with CMV was confirmed by detection of CMV DNA by polymerase chain reaction amplification in 15 patients (all of whom were negative by culture), by culture in one patient, and by objective clinical response to anti-CMV treatment in one patient. Only nine patients had a CSF pleocytosis 28-1142 (median 150) cells/mm3; in seven there was a polymorphonuclear (PMN) leucocyte preponderance. Protein concentrations in CSF were moderately or considerably raised in 13 patients; CSF: plasma glucose ratios were < or = 50% in five patients. Two patients had no pleocytosis, normal CSF: plasma glucose, and normal or near normal protein values. CONCLUSIONS: Abnormalities in CSF in CMV associated ALP are varied: only 50% of patients have a "typical" PMN preponderant pleocytosis. The diagnosis of this condition should not rely on demonstration of a PMN preponderant pleocytosis, but on identification of CMV DNA in CSF and the exclusion of other opportunistic infections and lymphoma in order that specific anti-CMV treatment may be instituted.

Quantitation of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid by competitive PCR in AIDS patients with different HCMV central nervous system diseases.

The current study was designed to quantitate human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) of persons with AIDS with specific HCMV-related CNS disease. DNA present in CSF obtained from AIDS patients was initially detected by a qualitative PCR procedure and then quantitated using a competitive PCR assay. In a group of 21 AIDS patients with HCMV-related CNS disease, 12 patients with HCMV polyradiculopathy had a mean +/- SEM of 11,982 +/- 4,480 copies/microliters in their CSF compared to 1,747 +/- 929 for 9 patients with HCMV encephalitis p = 0.017). Of the 14 patients with > 1,000 copies/microliters of HCMV DNA in CSF, 11(79%) had HCMV polyradiculopathy including all 3 with > 10,000 copies/microliters. Ganciclovir treatment of 3 patients with HCMV-related CNS disease was associated with a decline in HCMV DNA detectable within CSF. These data indicate that quantities of HCMV DNA in CSF are higher in persons with HCMV-related polyradiculopathy than encephalitis, and that quantitation of HCMV DNA can be useful in monitoring antiviral therapy.

Clinical spectrum of neurological herpes simplex infection.

All cases of neurological infections virologically verified as due to herpes simplex virus (HSV) during a 2-year period in the Helsinki University Hospital area were studied. Altogether 10 cases were divided clinically into two forms: encephalitis 5 cases, polyradiculomyelitis, meningitis and miscellaneous 5 cases. All the cases of encephalitis were treated with acyclovir. None of the severe cases of herpes radiculomyelitis received this drug, because of lack of a rapid virological diagnosis. Besides encephalitis HSV was associated with other types of severe diseases and those need attention for proper therapy.

Neurosyphilis in AIDS patients: initial CSF VDRL may be negative.

We report 2 HIV-seropositive patients with neurosyphilis whose initial CSF VDRL tests were negative. The CSF VDRL became positive after 12 days of IV penicillin treatment for syphilitic meningitis in the 1st patient. The 2nd patient developed syphilitic polyradiculopathy and a positive CSF VDRL 3 months after treatment with IV penicillin. Serial CSF VDRL determinations may be required in AIDS patients when a diagnosis of neurosyphilis is suspected.

Elsberg syndrome: a neurologic basis for acute urinary retention in patients with genital herpes.

Three patients with genital herpes simplex type II primoinfection and acute urinary retention are described. All patients showed pleocytosis of the cerebrospinal fluid, substantiating central nervous involvement. The association of genital herpes and sacral (myelo-) radiculitis has gained little attention in gynecologic literature, yet it is not an uncommon finding in female patients suffering from herpes. The present report emphasizes the importance of urinary symptoms in genital herpes and reviews the literature on similar cases.

Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth's syndrome).

The conditions of 5 patients with untreated lymphocytic meningoradiculitis (Bannwarth's syndrome, probably equivalent to Lyme disease) with serologically confirmed infection resulting from Borrelia spirochetes were followed with repetitive lumbar punctures up to 221 days after the onset of symptoms. Using a protein A plaque assay, high numbers of IgG-, IgM-, and IgA-producing cells were found in the cerebrospinal fluid (CSF), whereas there were mostly normal numbers of immunoglobulin-producing cells in peripheral blood. A markedly increased CSF IgM index and an elevated IgG index were observed in all patients during the early phase, reflecting production of these immunoglobulins within the central nervous system. All patients had oligoclonal IgG bands in the CSF that persisted during follow-up; in the 2 patients tested, the bands contained Borrelia antibodies. Most serum immunoglobulin concentrations were normal and in only 1 patient was it possible to detect in serum some of the oligoclonal IgG bands present in CSF. Declining numbers of CSF cells producing immunoglobulin and decreasing immunoglobulin index values were observed during follow-up, but 3 patients had an elevated CSF IgM index in the presence of normal IgG and IgA indices when examined during the later phases of disease. An intense and prolonged IgM response within the central nervous system seems to be a characteristic of the disease.

Agarose isoelectric focusing, antiserum immunofixation and silver staining for detection of oligoclonal bands in unconcentrated cerebrospinal fluid.

Unconcentrated cerebrospinal fluid (CSF) and corresponding serum from 30 patients with multiple sclerosis (MS), 30 with other neurological disease and 30 controls suffering from tension headache or psychoneurosis, were examined for oligoclonal IgG bands by initial separation employing agarose isoelectric focusing (AIF) followed by a modified procedure of immunofixation with monospecific antiserum and silver staining. This method is specific for demonstration of IgG and has a limit for detection of 0.4 microgram of IgG. Comparing the results with those obtained by AIF followed by capillary blotting to nitrocellulose membrane, double antibody peroxidase labeling and avidin-biotin amplification, both methods revealed similar frequencies of positive findings for oligoclonal IgG bands in the three patient groups. AIF followed by antiserum immunofixation and silver staining is a simple, sensitive and specific method for detection of oligoclonal IgG in unconcentrated CSF.

[Characteristic cerebrospinal fluid findings and clinical aspects of lymphocytic meningoradiculitis]. / Charakteristische Liquorbefunde und Klinik der lymphozytären Meningoradikulitis.

Clinical data and Cerebrospinal fluid (CSF) findings of 20 patients suffering from a meningoradiculitis were analyzed. Most patients had a tick bite or an erythema migrans before neurological symptoms occurred. All suffered from severe radicular pain. Predominant neurological symptoms were peripheral palsies of the facial nerve followed by motor paresis of the trunk and the extremities of mostly asymmetric distribution. Predominant CSF alterations were a long lasting inflammatory cellular reaction and an impairment of the blood-CSF barrier. In contrast to the CSF of 17 patients suffering from a polyradiculitis Guillain Barré with a similar total protein content, an intrathecal immunoglobulin IgG synthesis could be confirmed for the majority of the patients. CSF finding would be compatible to a viral as well as a borrelia etiology.