Cerebrospinal fluid IgG changes in subacute sclerosing panencephalitis in the various stages of the disease and during isoprinosine therapy

The cerebrospinal fluid (CSF) levels of IgG and the separation of the CSF and serum proteins by isoelectric focusing (IEF) were studied in 5 patients with subacute sclerosing panencephalitis (SSPE). Oligoclonal IgG fractions were found in the CSF of all the patients. The CSF IgG, IgG-Index and IgG SYN values were higher in the patients observed in the earlier than in those seen in the later stages of the disease. 1 of the 3 patients treated with isoprinosine presented a partial clinical remission accompanied by an increase in the parameters of intrathecal IgG synthesis.

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Sommario In 5 pazienti affetti da panencefalite sclerosante subacute (PESS) sono stati studiati i livelli liquorali di IgG ed il frazionamento delle proteine liquorali e sieriche mediante isoelettrofocalizzazione (IEF). In tutti i pazienti sono state riscontrate frazioni di IgG oligoclonali nel liquido cerebrospinale (LCS). Nei soggetti giunti alla osservazione in fasi della malattia più precoci si sono osservati valori di IgG liquorali, di IgG-Index e di IgG SYN più elevati rispetto agli altri in stadio più avanzato. Uno dei tre pazienti trattati con Isoprinosina ha presentato una parziale remissione clinica, accompagnata da incremento dei parametri di sintesi intratecale di IgG.

     

Peripheral neuropathy in CADASIL

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary cerebral microangiopathy associated with mutations in the Notch 3 gene. The clinical phenotype is characterized by cerebral impairment even though typical microvascular changes are diffuse. Objective To assess peripheral neuropathy in patients with CADASIL. Patients and Methods We enrolled eleven CADASIL patients with variable phenotype including clinical signs of peripheral nerve involvement. In all patients electromyography and nerve conduction velocities were performed. Peripheral nerve biopsy was performed in three cases. Results We found sensory motor neuropathy in 7/11 patients. Nerve biopsy revealed axonal and demyelinated findings. Conclusion Our findings suggest that peripheral neuropathy may be part of the CADASIL phenotype.     

Peripheral neuropathy in young-old and old-old patients.

Diabetes is said to account for most cases of neuropathy in the elderly. We reviewed records of 223 young-old (65-79 years) and 77 old-old (>or=80 years) patients referred for evaluation of neuropathic symptoms over a 9-year period. We prospectively validated our findings in 102 consecutive elderly (77 young-old) patients receiving intensive evaluation for neuropathy. Diabetes was the most common cause of neuropathy (41%), but was less common in the old-old (25% versus 46%, P < 0.001). Idiopathic neuropathies were more common in the old-old (39% versus 9%, P < 0.001). Alcoholic and nutritional neuropathies were uncommon in the old-old. Electrophysiological studies showed that most patients had an axonal type of neuropathy. Sural and peroneal response amplitudes were poorly correlated with age. We obtained similar results in our prospective study. The distribution of causes of neuropathies in young-old and old-old patients, in a hospital-based sample, is age-related. Future studies need to include the old-old to better understand the nature of neuropathy in the elderly.     

Cyclosporin A therapy in paraprotein-associated neuropathy.

A case of IgG paraprotein-associated demyelinating neuropathy complicated by respiratory failure, which was unresponsive to standard immunosuppressive drug therapy, is reported. Cyclosporin A therapy resulted in a marked clinical recovery with objective improvement in nerve conduction and vital capacity. The beneficial response suggests that cell-mediated immunity is an important pathogenetic mechanism, and that cyclosporin A may be useful in the treatment of other refractory cases of paraprotein-associated neuropathy.     

Silver staining of cerebrospinal fluid IgG in isoelectric focusing gels

A silver staining technique to be used on isoelectric focusing (IEF) gels for cerebrospinal fluid (CSF) oligoclonal IgG bands is described. The technique provides a sensitivity for detection of greater than 0.17 micrograms of IgG. The additional use of immunofixation with anti-human IgG antiserum rather than chemical fixation improves the sensitivity two-fold and permits identification of the oligoclonal bands as IgG. The technique enables one to focus small volumes of unconcentrated CSF (less than 40 microliters) and provides a powerful research tool.     

Immunoperoxidase staining of cerebrospinal fluid IgG in isoelectric focusing gels: a sensitive new technique

An isoelectric focusing (IEF) technique using direct peroxidase or peroxidase-antiperoxidase (PAP) overlay staining for detection of cerebrospinal fluid (CSF) oligoclonal IgG is described. The method involves chemical fixation of all proteins in the gel followed by application of peroxidase coupled antiserum as a specific stain. The direct peroxidase system is 4 times and the PAP system 8 times as sensitive as Coomassie blue staining after standard IEF or Coomassie blue staining of immunofixed gels. As little as 0.5 microgram (direct peroxidase) or 0.3 microgram (PAP) of IgG can be detected. Direct peroxidase staining of IgG in IEF gels can be used to examine unconcentrated CSF, with banding patterns similar to those obtained by Coomassie blue staining after standard IEF of concentrated CSF.     

Peripheral neuropathy in Cockayne syndrome

Two siblings with Cockayne syndrome are reported. In one case a sural nerve biopsy showed a demyelinating peripheral neuropathy with occasional inclusions in Schwann cells made up of electron dense finely granular material intermingled with vacuoles or lamellar structures. The significance, if any, of this accumulated material remains unclear. The presence, in addition, of small finely lamellar intra-axonal osmiophilic bodies suggests an associated axonal involvement

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Sommario Vengono descritti due casi di Sindrome di Cockayne. In un caso è stata effettuata una biopsia del nervo surale che ha evidenziato una neuropatia periferica di tipo demielinizzante con rare inclusioni nelle cellule di Schwann, formate da materiale osmiofilo finemente granulare, vacuoli e strutture lamellari. Il significato di tali inclusioni è molto incerto. La presenza inoltre di corpi osmiofili lamellari intrassonali suggerisce una associata compromissione assonale.

     

Cerebrospinal fluid variables among alcoholics lack seasonal variation.

Seasonal influences on indices of serotonergic function, including cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), have been reported in psychiatric patients and healthy volunteers. We examined seasonal differences in CSF concentrations of 5-HIAA among 135 alcoholics admitted to a research ward who had a lumbar puncture. No significant seasonal differences were found for either CSF concentrations of 5-HIAA or CSF concentrations of other monoamine metabolites or peptides. The possible explanations for these negative findings are discussed.     

Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literature

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.     

Cerebrospinal fluid and peripheral blood T-lymphocyte subsets in multiple sclerosis: monoclonal antibody analysis and correlations with clinical activity

Enumeration of cerebrospinal fluid and peripheral blood T-lymphocyte subsets (T-total, T-helper and T-suppressor) was performed by monoclonal antibody technique in 18 patients with Multiple Sclerosis and in 4 patients with non-inflammatory neurological diseases. While no differences were observed in peripheral blood subsets among the various phases of the disease, a marked rise in cerebrospinal fluid helper-suppressor ratio was seen in acute relapses. The results give further support to the concept of a strict compartimentalization in immune response abnormalities in Multiple Sclerosis patients.

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Sommario Sono state studiate con anticorpi monoclonali le sottopopolazioni linfocitarie (T-totali, T-helper e T-suppressor) ematiche e liquorali in 18 pazienti con sclerosi multipla e 4 con malattie neurologiche non infiammatorie. Non è stata trovata alcuna differenza del rapporto helper/suppressor nel sangue in varie fasi della malattia, mentre un aumento del rapporto helper/suppressor nel liquor è stato riscontrato nelle riesacerbazioni. I risultati confermano la compartimentalizzazione delle anomalie della risposta immunitaria nella sclerosi multipla.

     

Cerebrospinal fluid lymphocyte subpopulations in multiple sclerosis

T3+ (all-T) and T8+ (suppressor/cytotoxic) cells were studied in cerebrospinal fluid (CSF) from 24 patients with multiple sclerosis (MS) and from 24 subjects with various non-immunological diseases (NID). MS patients were classed as (a) during the acute phase of the 1st espisode of the disease, (b) in acute relapse, (c) with chronic progressive disease, (d) with increased or (e) normal CSF IgG content or (f) with neurological impairment (Kurtzke scale) 3 or (g) >3. In MS cases considered as a whole a significant decrease in CSF T3+ cells was found compared to NID patients. When single groups were considered, T3+ cells decrease was significant in classes (b), (d) and (f). Significantly lower percentages of T8+ cells, compared to NID, were found in MS classes (a), (d) and (f).

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Sommario Sono stati studiati i linfociti identificabili con anticorpi monoclonali T3 (T totali) e T8 (T soppressori/citotosici) nel liquor di 24 pazienti affetti da sclerosi multipla (SM) e di 24 soggetti affetti da malattie non immunologiche (NID). I pazienti con SM sono stati suddivisi secondo i seguenti parametri: (a) in fase acuta del 1° episodio della malattia, (b) in recidiva, (c) con malattia cronica progressiva, (d) con contenuto liquorale di IgG aumentato o (e) normale, (f) con gravità neurologica (scala di Kurzke) 3 o (g)>3. Nel complesso dei casi di SM, venne trovata una significativa diminuzione dei linfociti T3+, rispetto ai controlli. Prendendo in considerazione i singoli gruppi, i linfociti T3+ erano significativamente ridotti nei casi di SM in recidiva, con IgG liquorali aumentate con gravità neurologica >3. Invece, percentuali significativamente più basse di linfociti T8+ vennero trovate nei casi di SM durante la fase acuta del 1° episodio, con IgG liquorali aumentate, con gravità neurologica 3.

     

Cerebrospinal fluid adrenaline and noradrenaline in depressed patients

Mean adrenaline concentration in cerebrospinal fluid measured by a sensitive and specific isotope-derivative assay was significantly lower in 15 depressed patients during illness compared with 18 control subjects. At the time of recovery cerebrospinal adrenaline levels had increased markedly to normal levels. Cerebrospinal fluid noradrenaline did not differ in patients compared with controls. The present findings suggest that adrenaline as a neurotransmitter may be involved in affective disorders.     

Cerebrospinal fluid enzymes in neurological diseases

The activities of adenylate kinase, creatine kinase and lactate dehydrogenase were measured in cerebrospinal fluid and serum from 127 patients admitted to the Department of Neurology. All cerebrospinal fluid samples with hemoglobin greater than 1 mg/l were excluded. Upper reference limits for the enzyme determinations were established, using samples from patients without objective criteria of organic involvement of the nervous system. High enzyme activities did not correlate to any particular group of diseases and were also found in patients without organic brain diseases. We conclude that determination of the three enzymes in cerebrospinal fluid is of limited value in the diagnosis of neurological diseases.     

Peripheral neuropathy in myotonic dystrophy type 1

Myotonic dystrophy 1 (DM1) is characterized by a wide range of clinical features. We aimed to verify the presence of peripheral nerve involvement in a large cohort of DM1 patients and to determine clinical consequences. A total of 93 patients underwent detailed neurological examination and nerve conduction studies. Additionally, balance impairment was assessed with the Berg Balance Scale and health status was evaluated with the SF-36 health survey. Sensory symptoms were not reported and mild sensory signs were found in six patients. Electrophysiological abnormalities consistent with a diagnosis of neuropathy were found in 16 patients (17%). Peripheral nerve involvement was significantly associated with decreased muscle strength (p = 0.001) and absence of Achilles-tendon reflexes (p = 0.003), but not with age or duration of neuromuscular symptoms. It had no significant effect on balance, mental or physical health. In conclusion, peripheral nerve involvement may be one of the multisystemic manifestations of DM1, but is usually subclinical. Other causes should be excluded when sensory symptoms or signs are severe.     

Cerebrospinal fluid monoamine metabolites in alcoholic patients who attempt suicide.

Reduced cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid have been reported to be commonly associated with suicidal behaviour. Alcoholics are known to often manifest suicidal behaviour. Therefore, we compared cerebrospinal fluid levels of monoamine metabolites in alcoholics who had (n = 20) and had not (n = 108) attempted suicide and healthy volunteers (n = 30). There were no significant differences among the 3 groups for CSF levels of either 5-hydroxyindoleacetic acid, the dopamine metabolite homovanillic acid, norepinephrine, or the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol.     

Neurological monitoring reduces the incidence of bortezomib-induced peripheral neuropathy in multiple myeloma patients

Bortezomib (BTZ) is a proteasome inhibitor approved in the treatment of multiple myeloma (MM). Bortezomib-induced peripheral neuropathy (BIPN) is an unpredictable dose-limiting adverse event in one-third of patients. In the present study, 58 relapsed/refractory MM patients treated with BTZ were analyzed. The study's aim was to compare BIPN incidence and severity between both groups and to identify risk factors of BIPN. Twenty-four MM patients were evaluated by a neurologist periodically during BTZ treatment in order to prevent high-grade BIPN. Thirty-five MM patients previously treated with BTZ were reviewed. Seven (29%) patients in the monitored group and 19 (56%) in the historical cohort developed BIPN (p = 0.044). In the univariate analysis, factors related to BIPN in the whole series were age, number of vincristine and BTZ cycles, lactate dehydrogenase and neurological monitoring. Multivariate analysis revealed that absence of neurological monitoring (Hazard Ratio [HR]: 4.94 IC 95% [1.31–18.68], p = 0.019) and prior treatment with vincristine (HR: 1.34 IC 95% [1.04–1.74], p = 0.026) were associated with greater risk of BIPN. Baseline total neuropathy score-clinical version (TNSc) was a good predictor of BIPN, with higher risk for patients with TNSc >2 (p = 0.038). Neurological monitoring is useful for diminishing BIPN. Neurological monitoring of patients with baseline TNSc >2 should be considered.     

Peripheral neuropathy in systemic lupus erythematosus – a longitudinal study

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. Subjects and Methods: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.     

Peripheral neuropathy in individuals with HIV infection in Zimbabwe

Peripheral neuropathy is associated with HIV infection. The prevalence and types of peripheral neuropathy encountered in a randomly-selected HIV infected African population at different stages of disease were investigated. HIV positive individuals were categorized into 1 of 3 groups: asymptomatic, symptomatic and AIDS. HIV negative individuals formed the control group. Nerve conduction data were obtained using standard electrophysiological procedures and CD4⁺ levels were measured. The type of neuropathy was determined from the history, clinical presentation and electrophysiological abnormalities. The prevalence of peripheral neuropathy was 44%: subclinical neuropathy (SCN) accounted for 56%, acute inflammatory demyelinating polyneuropathy (AIDP) for 15% and distal symmetrical polyneuropathy (DSPN) for 22% of cases of neuropathy. SCN was found in all categories whereas AIDP predominated in the symptomatic category and DSPN in individuals with AIDS. The pattern and frequency of neuropathies seen in our African population is similar to that reported from other continents.     

Cerebrospinal fluid dynamics and long-term survival of the Strata valve in idiopathic normal pressure hydrocephalus

Lundkvist B, Koskinen L‐OD, Birgander R, Eklund A, Malm J. Cerebrospinal fluid dynamics and long‐term survival of the Strata^® valve in idiopathic normal pressure hydrocephalus.
Acta Neurol Scand: 2011: 124: 115–121.
© 2010 John Wiley & Sons A/S. Objective – Cerebrospinal fluid (CSF) dynamics and long‐term shunt survival of the Strata^® CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). Subjects and methods – Seventy‐two patients with INPH received a Strata^® valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long‐term shunt survivals were obtained from patient records. Results – The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty‐nine patients (72%) had an improved gait. Two patients were improved despite non‐functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6‐month follow‐up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. Conclusions – The long‐term survival of the Strata^® valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti‐siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.     

Cerebrospinal fluid analysis differentiates multiple system atrophy from Parkinson's disease.

We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinson's disease (PD; n = 35) and multiple system atrophy (MSA; n = 30). The median CSF concentration of the neurotransmitter metabolites 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49-70%) in MSA compared to PD. In contrast, several brain-specific proteins (tau, neuron-specific enolase, myelin basic protein) were elevated (130-230%) in MSA compared with those in PD. A combination of CSF tau and MHPG discriminated PD from MSA (adjusted odds ratios: tau, 27.2; MHPG, 0.14). Our data suggest that the more progressive and widespread neurodegenerative nature of MSA, as compared with PD, is reflected in the composition of CSF. We propose that CSF analysis may become part of the diagnostic work-up of patients with parkinsonian syndromes.