Penile and perianal pudendal nerve somatosensory evoked potentials in the diagnosis of erectile dysfunction.

Neurophysiologic examinations in differential diagnosis of erectile dysfunction comprise electromyogramme of the pelvic floor, pudendal nerve terminal motor latency (PNTML) and evaluation of pudendal somatosensory evoked potentials (SSEP). We focused our interest on comparing diagnostic importance of penile and perianal pudendal nerve SSEP. We examined 20 patients suffering from erectile dysfunction and 20 patients without any manifestation of impotence. The stimulus was administered using penile ring electrodes at the base of the penis (cathode) and distally on the penis shaft (anode), as well as a perianal surface electrode applied at 3 o'clock in lithotomy position and 5 cm laterally on the gluteal skin. The potentials were recorded with intradermal needle electrodes at C(z)-2 cm (different) and F(z) (indifferent). 500 stimuli were averaged for a single tracing. The stimulus strength was set at an average of 3-4 times the stimulus threshold. Cortical latency of P 40 ranged from 39.0 to 45.6 ms (penile) and from 33.6 to 43.2 ms (perianal) in the control group, in the patient group latencies ranged from 38.8 to 51.6 (penile) and 34.0 to 44.8 ms (perianal). In two patients no potential was recordable after perianal stimulation, one patient showed a marked prolongation of the penile response with a normal perianal latency. Penile and perianal latencies of P 40 were significantly prolonged in the patient group compared to the control group (P<0.05). The combination of penile and perianal pudendal SSEP may provide valuable additional information in differential diagnosis of erectile dysfunction, especially allowing to identify different sites of neurogenic lesions. In contrast to perianal pudendal SSEP, penile stimulation may help to discover pathologic changes in the distal course of the pudendal nerve, especially the dorsal nerve of the penis.

IgG-mediated cytotoxicity to myenteric plexus cultures in patients with paraneoplastic neurological syndromes.

Autoantibodies against neuronal and tumour proteins have been described in many paraneoplastic neurological syndromes (PNS), but it is not clear whether these antibodies are pathogenic or simply a useful diagnostic tool. We took seven sera that were positive on routine screening for antineuronal antibodies and the IgG fractions. As controls we used sera from health blood-donors, other neurological autoimmune diseases and patients with SCLC without PNS. We tested them on dissociated rat myenteric plexus cultures for cytotoxic effects. After incubation for 24 h, cytotoxicity was determined by a double fluorescence test (calcein green for living cells and ethidium homodimer-1 for dead cells). We found an increased cell death rate in cultures incubated with the PNS sera, compared with all controls (P< 0.05). Isolated IgG fractions were also cytotoxic whereas the IgG-free serum fraction did not show any significant increase in cytotoxicity. After incubation with PNS IgG, FACS analysis revealed an increased cytotoxicity rate only of the neurones, but not the glial cells. Our results indicate that in PNS a complement-independent, antibody-mediated cytotoxicity against neurones may contribute to the pathogenesis of these syndromes.

Antineural and antinuclear autoantibodies are of prognostic relevance in non-small cell lung cancer.

BACKGROUND: Autoantibodies against nervous system structures have been proven to be a prognostic factor in small cell lung cancer. However, little is known about humoral autoimmunity in non-small cell lung cancer (NSCLC) and its prognostic significance. METHODS: We examined antineural antibodies (AnAb) and antinuclear antibodies (ANA) in the sera of 61 patients with NSCLC (histologically: 29 adenocarcinoma, 32 squamous cell carcinoma). Twenty-one patients had stage I NSCLC, 11 stage II, and 29 patients stage III. Autoantibody detection was done by immunofluorescence test; Western blotting was used as a confirmation test. RESULTS: Of the NSCLC patients, 27.8% were antineural antibody positive, and 32.7% had ANA. No differences were found between the histological groups. AnAb-positive patients showed a better survival in all patients (p = 0.005). There was also a higher survival of ANA-positive patients, but this was only significant in stage III (p = 0.0025). Cox regression analysis showed that antineural and antinuclear antibodies are a stage-independent prognostic factor in NSCLC. CONCLUSIONS: Antineural and antinuclear autoantibodies are a stage-independent prognostic factor in patients with NSCLC and may represent an effective immune response to the tumor.

Shift in the IgG subclass distribution in patients with lung cancer.

Lung cancer patients have been reported to have generalized immune dysfunction of the cell-mediated immune response. In contrast, little is known about the humoral immune function in these patients. Therefore, we examined the IgG subclass distribution (IgG1-lgG4) in 67 lung cancer patients (23 adenocarcinoma, 29 squamous cell carcinoma, 15 small cell carcinoma), 13 patients with inflammatory lung diseases, seven patients with pulmonary metastasis and 23 healthy controls using a commercial available ELISA. We found a significant increase in the percentage of IgG1 in adenocarcinoma, compared with squamous cell and small cell lung carcinoma (P < 0.05). Small cell lung cancer patients showed an increase in IgG2, IgG3 and IgG4 compared with all other groups (P < 0.05, respectively). IgG1/lgG2, IgG1/lgG3 and IgG1/lgG4 ratios in adenocarcinoma were higher than in small cell lung cancer (P < 0.05). In the squamous cell carcinoma there was no difference in IgG subclass distribution compared to controls. Our study demonstrates that the different histological subtypes of lung carcinoma influence the IgG subclass distribution. Whether this phenomenon is the result of a direct influence on B-cell activity by the tumor needs further investigation.

Intravenous immunoglobulins in the therapy of paraneoplastic neurological disorders.

The treatment of paraneoplastic neurological syndromes (e.g., tumor therapy, immunosuppressive therapy, plasmapheresis) rarely leads to an improvement in the neurological symptoms. We treated four patients suffering from paraneoplastic neurological syndromes with intravenous immunoglobulins. All four had high titers of antineuronal antibodies in serum and CSF. Two of the patients, one suffering from paraneoplastic cerebellar degeneration and the other from paraneoplastic brain stem encephalitis and polyneuropathy, received intravenous immunoglobulin treatment within 3 weeks of the onset of neurological symptoms. Both patients showed clinical improvement within 2 weeks after the initiation of therapy. They also showed a decline in the intrathecal antibody synthesis of the antineuronal antibody. Two other patients, who had suffered from paraneoplastic neuropathy for 3 and 6 months showed no improvement with the intravenous immunoglobulin therapy. In these cases there was no effect on intrathecal antibody synthesis. When started early, intravenous immunoglobulins may be of therapeutical value in treating paraneoplastic neurological syndromes. Specific intrathecal antibody synthesis may be a better measure of clinical course that autoantibody serum titers.

[Value of antibody titers for diagnosis of neuroborreliosis]. / Wertigkeit von Antikörpertitern für die Diagnose einer Neuroborreliose.

Neuroborreliosis is a very frequent subtype of infection with Borrelia burgdorferi. Because of the widely spread inapparent infections finding of diagnosis by analysis of serum antibodies is very difficult. In the years 1990-1994 the serum of 6.775 patients of the Department of Neurology in Homburg, Germany was analysed with regard to Borrelia burgdorferi specific IgG antibodies. 24% showed a positive serum titer and 20% a borderline result. 73 patients showed a specific intrathecal IgG antibody synthesis. In contrast to patients with antibodies in serum these patients showed a significant cumulation during summer. The high percentage of positive serum titers and the season independence support the assumption of widely spread inapparent infections. If a patient shows neurological symptoms the finding of serum antibodies against Borrelia burgdorferi is not sufficient for the diagnosis of Neuroborreliosis. A specific intrathecal synthesis of antibodies, is the most reliable serological indicator for Neuroborreliosis. Intrathecal synthesis usually starts three to four weeks after the first clinical symptoms.

Variability of velocity and duration of microembolic signals detected by bigated transcranial Doppler sonography in carotid endarterectomy.

OBJECTIVE: To differentiate between gaseous and particular microemboli in carotid surgery one clinical approach is the interpretation of the effective sample volume length (SVL). We investigated whether such a clinical interpretation is based on reproducible measurements. METHODS: Microembolic signals (MES) recorded during carotid endarterectomy by a bigated transcranial Doppler device were analyzed off-line. In the two sample volumes, the duration and the velocity of the MES were measured by two observers independently from each other twice within 2 weeks. The SVL of the MES were calculated by multiplying duration with velocity. RESULTS: In the anatomical proximal sample volume 215 MES were recorded of which 203 (94.5%) were also present in the distal. The SVL medians of the MES were 2.2-4.1 mm lower in the distal than in the proximal sample volume as a result of lower velocity and shorter duration of the MES in the distal sample volume. The median of the paired differences of the SVL was 0.2 mm (interquartile range: 0.0-1.2) in the proximal sample volume and 0.8 mm (0.2-1.8) in the distal sample volume for observer 1, and 0.6 mm (0.4-2.2) and 0.9 mm (0.5-1.6) for observer 2. The median of the paired differences of the SVL between the observers was 1.4 mm (1.2-2.9) in the proximal sample volume and 1.6 mm (1.3-3.0) in the distal. CONCLUSION: The intra- and interobserver agreement on calculating SVL is good. However, the depth of insonation influences some features of embolic signals.

Influence of the angiographic internal carotid artery stenosis assessment method on indicating carotid surgery.

BACKGROUND: To estimate the influence of different kinds of angiographic internal carotid artery (ICA) stenosis assessment methods on clinical decision making on carotid surgery. METHOD: One hundred angiographically proven ICA lesions in 65 patients (54 men, 11 women, mean age +/- SD, 64 +/- 8 years) were evaluated by simultaneous biplane angiography. The angiograms were analyzed using three kinds of linear diameter reduction methods [North American (NASCET), and European (ECST) carotid surgery trial method, common carotid artery method (CC)], and five area reduction methods reflecting more accurately the anatomical degree of stenosis [squared NASCET, ECST and CC (N2, E2, CC2), combined stenosis estimation of two projections (NASCET-bi, ECST-bi)]. All lesions were additionally evaluated by continuous wave (cw-)Doppler ultrasound prior to angiography. Between method agreement on classifying the lesions into stenosis < 70% and into stenosis > or = 70% was calculated by means of kappa statistic. RESULTS: The degree of stenosis (median and inter-quartile range) ranged between 65% (38-82) by means of NASCET and 91% (87-93) by means of CC2. Thirty-seven ICA stenoses would have been operated on using NASCET, but 82 using CC2. Between method agreement on assessing high grade ICA stenosis ranged from poor (kappa value 0.17 for the pair NASCET/CC2) to excellent (kappa value 0.92 for the pair N2/NASCET-bi). Cw-Doppler ultrasound showed a good agreement (kappa value 0.72-0.80) with all angiographic methods using an area reduction formula apart from CC2. The agreement was moderate between cw-Doppler and NASCET and ECST, respectively. CONCLUSION: The clinical decision to operate on an ICA stenosis will strongly be influenced by the angiographic method used. Because reliable clinical data exist only for the NASCET and ECST method these two angiographic stenosis assessment method should be used for clinical decision making.

Antineuronal antibody-associated paraneoplastic neuropathy in Hodgkin's disease.

Paraneoplastic neurological syndromes in patients with Hodgkin's disease are rare findings. Subacute, paraneoplastic cerebellar degeneration or autonomic dysfunctions were described before. In some of these cases, autoantibodies against central or peripheral nervous system structures were found in serum and CSF. We present a 30-year-old white male who developed a progredient, clinical and electrophysiological distal sensomotoric neuropathy. Six months after the beginning of the neurological disturbances, Hodgkin's disease (Stadium III BE) was diagnosed. Other reasons for neuropathy, such as direct impairment of the peripheral nervous system by tumor masses or drug-induced neuropathy, were excluded. Cerebrospinal fluid (CSF) analysis showed a mild pleocytosis, elevated total protein (9.8 g/l) and identical oligoclonal bands in serum and CSF. Blood-CSF barrier damage was detected by Reiber formula. Indirect immunofluorescence and western blot analysis demonstrated an autoantibody against peripheral and central nervous system structures in serum and CSF. Although the autoantibody responded to a 38-40 kDa-protein in western blot and showed nuclear staining of myenteric plexus and Purkinje cell nuclei in the immunofluorescence test, this antibody was shown to be not identical to anti-Hu. An intrathecal synthesis of the antineuronal antibody was detected by antibody specificity index. Tumor therapy, plasmapheresis and treatment with intravenous immunoglobulins did not improve the neuropathy. According to our knowledge this is the first case of antineuronal antibody-associated sensomotoric neuropathy in Hodgkin's disease.

Hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy: report on a family.

We describe two siblings affected by a motor and sensory neuropathy starting in childhood. Already in infancy, a spastic gait disturbance had become obvious, leading later to multiple surgical interventions. In adolescence, progressive loss of vision developed. At the time of our examination, both siblings showed severe weakness and atrophy of the distal muscles of legs and arms. Tendon jerks were brisk in proximal muscles; in the lower extremities, muscle tone was increased. Visual acuity was severely decreased. Nerve conduction studies revealed an axonal degeneration. This finding was confirmed by evaluation of a sural biopsy specimen in one patient, showing only few remaining myelinated fibres without signs of demyelination. This combination of hereditary motor and sensory neuropathy with spastic paraplegia and optic atrophy shows features of both hereditary motor and sensory neuropathy V and VI according to the classification of Dyck, indicating that these subtypes may not represent distinct entities.

Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease--effect of L-Dopa.

There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).

[Intracerebral hemorrhage and multiple brain abscesses caused by Bacillus cereus within the scope of acute lymphatic leukemia]. / Intrazerebrale Blutung und multiple Hirnabszesse durch Bacillus cereus im Rahmen einer akuten lymphatischen Leukämie.

Multiple hematogenic brain abscesses in immunosuppression are occasionally caused by rare and primary apathogenic causative agents. We report a first case of an isolated CNS infection by Bacillus cereus, which led to death from multiple brain abscesses and an intracerebral hemorrhage, probably caused by the infection, within 4 days. The underlying disease leading to immunosuppression was acute lymphatic leukemia in complete remission. In spite of antibiotic therapy the chemotherapy-induced neutropenia enabled unhindered spreading of the necrotizing infection, which was verified by histological analysis. The production of potent toxins such as hemolysin and cerelolysin by B. cereus leads to rapid and fulminant tissue destruction usually involving the walls of blood vessels.

Therapy of anal fissure using botulin toxin.

PURPOSE: With chronic anal fissure, sphincterotomy to relieve sphincter spasm is the recommended therapy. This breaks the vicious circle of inflammation-pain-spasm. This obvious success is weighed against the possible risk of the operation and the risk of subsequent fecal incontinence. The following report describes a therapy for anal fissure involving injection of the external anal sphincter with botulin toxin. METHODS: We have used this new method in 12 cases (7 females and 5 males; mean age, 37 years). We injected 0.1 ml of diluted toxin on both sides lateral to the fissure. RESULTS: The fissure healed thanks to a time-limited paresis of the sphincter in ten cases. In one case there was a recurrence within the first six months. Two patients could not be healed and had to undergo surgery. CONCLUSION: Injection of botulin toxin gives us a possible new mode of therapy in the treatment of chronic, uncomplicated anal fissures with increased sphincter tone. It is well tolerated, can be performed as an outpatient, does not cause any lesion of the continence organ, and subsequently does not lead to any permanent latent or apparent fecal incontinence.

[Schizophreniform psychosis in paraneoplastic limbic encephalitis]. / Schizophreniforme Psychose bei paraneoplastischer limbischer Enzephalitis.

Paraneoplastic limbic encephalitis is seldom mentioned in the psychiatric literature and premortem diagnosis is rare. Affective symptoms, agitation, and memory impairment are the core features, which can predate the diagnosis of carcinoma. We report the case of a patient with bronchial carcinoma, whose clinical picture could hardly be distinguished from that of endogenous schizophrenia.

[Brain metastases as an initial manifestation of tumor disease]. / Hirnmetastasen als Erstmanifestation einer Tumorerkrankung.

A retrospective study compared a group of 122 patients with brain metastases from unknown primaries with a second group of 121 patients, who developed brain metastases in the course of a known malignant disease. Special attention was paid to the kind of primary cancer, therapeutic influences and prognostic differences. The results pointed to a late occurrence of brain metastases in breast cancer, no patient with this type of cancer being found in group 1. Melanoma and colorectal cancer were also found predominantly in group 2, whereas lung cancer was the most common cause of metastasis in group 1 and the most frequent cancer in both groups. Clinical course, therapy and outcome showed no significant differences between the two groups. Mean survival time was 4.6 (+/- 6) months for the patient series as a whole. Patients with breast cancer had a significantly higher survival rate than those with other forms of cancer. Localisation and degree of malignancy mainly determine the life-prognosis, the type and intensity of therapy being of secondary importance.

Spastic disorder in patients with hereditary multiple exostoses, but without spinal cord compression: a new syndrome?

We describe a 37 year old man with a history of a gait disorder which had been worsening over a period of three years. Clinical examination showed the typical signs of a spastic tetraparesis with increased tone of all the extremities. Sensation, autonomic and cerebellar functions were not disturbed. Multiple exostoses had been present since early childhood, but none had been found in the spine or the cranium to cause the tetraspastic disorder. MRI scan was normal. Pedigree analysis of four generations showed that other family members were affected by both disorders. Chromosomal analysis was normal. We consider this to be a previously unknown hereditary syndrome transmitted as an autosomal dominant and manifesting a combination of spastic tetraparesis and multiple exostoses.

[Basilar aneurysm in the cerebello-pontine angle. Case report with review of the literature]. / Basilarisaneurysma im Kleinhirnbrückenwinkel. Fallbericht mit Literaturübersicht.

The importance of vascular lesions in the cerebello-pontine angle is discussed with reference to a case report of a basilar artery aneurysm with typical clinical signs of cerebello-pontine angle lesion. A review of 29 cases of aneurysms with cerebello-pontine angle syndrome is given. The presented case is the twelfth reported basilar artery aneurysm in this region with the typical clinical syndrome.

[Long-term treatment of Lambert-Eaton syndrome by 3, 4 diaminopyridine]. / Traitement au long cours du syndrome de Lambert-Eaton par la 3,4 diaminopyridine.

A patient with a 5 year history of slow-progressive Lambert-Eaton Myasthenic Syndrome (LEMS) was treated for a period of 12 months with 3,4-diaminopyridine (3,4-DAP). The therapy led to an objective increase in muscle power. During the treatment period, there was no increase in muscle weakness, but attempts at withdrawal of the drug confirmed a progression. The mouth dryness disappeared and autonomic regulation disturbances were improved. All of the laboratory parameters remained unchanged. A neoplasia was excluded by extensive endoscopic and radiological investigations. Side-effects included initial perioral paresthesia and, later, paresthesia down the skin and along the ulnar edge of the forearm. 3,4-DAP seems to be an effective and acceptable long-term symptomatic therapy in LEMS.