Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens.

The aims of the present study were to investigate how changes in the cumulative dose and the frequency of dosing influence the short-term antiresorptive efficacy of oral ibandronate treatment and whether serial measurements of bone markers could provide a useful diagnostic tool for the revelation of noncompliance to established treatments with antiresorptive drugs. Study participants were 200 healthy women 50-70 years old (mean 63.1 years) with a lumbar spine BMD t-score of -1 to -5. Women were randomly allocated to receive treatment with oral ibandronate according to one of the following eight dosing regimes: (1) 2.5 mg daily for 84 days; (2) 20 mg weekly for 84 days; (3) 2.5 mg daily for 28 days + no treatment for 56 days; (4) 2.5 mg daily for 28 days + 2.5 mg weekly for 56 days; (5) 2.5 mg daily for 28 days + 2.5 mg three times weekly for 56 days; (6) 2.5 mg daily for 14 days + 2.5 mg three times weekly for 56 days; (7) 2.5 mg three times weekly for 84 days; (8) no treatment for 168 days. Study parameters were the serum concentration of the C-terminal telopeptide of collagen type I (s-CTX, resorption marker) and N-MID osteocalcin (formation marker) measured by enzyme-linked immunosorbent assay. Oral treatment with ibandronate 20 mg weekly (cumulative dose 240 mg) resulted in greater final inhibition in s-CTX and area under the curve (AUC) compared to the 2.5 mg daily treatment (cumulative dose 210 mg), indicating that as long as optimal doses are administered the frequency of dosing has secondary importance for overall efficacy. When the cumulative dose was 130 mg or less, the final degree of inhibition was still the function of the cumulative dose, but the overall efficacy estimated by the AUC was also under the influence of the frequency of dosing. These observations suggest that serial measurements of s-CTX may provide a useful diagnostic tool for the early revelation of suboptimal dosing or noncompliance to already optimized therapies with antiresorptive agents.

Human immunodeficiency virus antibodies in cerebrospinal fluid.

The relative concentrations of human immunodeficiency virus (HIV) antibodies in relation to equal IgG contents of 46 serum cerebrospinal fluid (CSF) samples from 32 patients were determined by serial dilution in an anti-HIV enzyme-linked immunosorbent assay (ELISA). The ratio of CSF and the serum HIV antibody concentration was expressed as QHIV = CSF dilution/serum dilution. QHIV is regarded as a parameter for specific intrathecal HIV antibody production. The QHIV ranged from 0.7 to 16. Six of seven patients with clinical signs of acquired immunodeficiency syndrome (AIDS)-related dementia (ARD), but only seven of 25 patients without clinical diagnosis of ARD showed a QHIV greater than 2.

Refractory period impairment in sural nerves of diabetics.

Polyneuropathy is a frequent complication in diabetics. In a non-selected group of 65 diabetics, 30 patients had clinical signs of neuropathy. These patients had more significant changes in electrophysiological parameters than patients without clinically evident polyneuropathy. Significant reduction of sural nerve conduction velocity was observed in 16 of 30 patients with and in 4 of 35 diabetics without clinical signs of polyneuropathy. Additional information was obtained when paired stimuli were applied and the test response latency was measured. Stimulus intervals of 3 ms gave the highest quota of information about involvement of the sural nerve. Significant prolongation of the test response in paired stimulation at intervals of 3 ms was found in 21 of 30 patients with clinically apparent diabetic polyneuropathy and in 16 of 35 diabetics without clinical signs of polyneuropathy.

Chronic borrelia encephalomyeloradiculitis with severe mental disturbance: immunosuppressive versus antibiotic therapy.

A 57-year-old male was repeatedly admitted to hospital because of complex neurological symptoms, including radicular pain, disturbance of micturition, seizures, and severely impaired mental state. The diagnosis was encephalomyeloradiculitis possibly of viral origin, and treatment with immunosuppressants was initiated. An alternating course with a tendency towards improvement ensued. Two and a half years after the occurrence of the initial symptoms, identification of specific antibodies in the blood and CSF led to the diagnosis of borreliosis with CNS involvement. High-dose therapy with penicillin rapidly reduced the symptoms, beginning with those of radicular pain and followed by an improvement of the mental state. Attention is directed to the wide spectrum of clinical symptoms of chronic borreliosis with CNS involvement. Previous reports that immunosuppression may result in some improvement but with a tendency towards relapse are confirmed. Our encouraging treatment results support those of other reports that penicillin therapy may lead to improvement even at late chronic stages in patients with severe CNS deficits.

Autonomic neuropathy in diabetics: comparison of cardiovascular tests, neurography, and cerebral refractory period of somatosensory evoked potentials.

Circulatory regulation tests--postural heart rate response (PHRR), Valsalva ratio, and reaction to sustained muscle exercise--, sural nerve neurography and cerebral refractory period (CRP) of median nerve evoked potentials were measured in 17 diabetic inpatients and correlated with their clinical signs of autonomic neuropathy (AN) and sensorimotor polyneuropathy (SN). Non-diabetic inpatients (without cardiovascular or related nervous disease) served as controls. The data of the diabetics and non-diabetic age- and sex-matched inpatients were significantly different for the PHHR measured by the 30:15 ratio, sural nerve conduction velocity and sural nerve refractory period, and CRP. The results correlated with the corresponding anamnestic signs. The PHRR showed abnormal values much more frequently than the sural nerve neurography or the CRP. No correlation was found between the signs of AN and those of SN or CRP. This stresses the need for a circulatory regulation test (preferably PHRR) in any diabetic when planning narcosis, as only these AN tests can reliably predict an increased cardiovascular risk in individual patients.

Intrathecal production of HIV antibodies in suspected AIDS encephalopathy.

Thirty-one serum and CSF samples from 21 HIV-antibody-positive patients with neurological deficits were examined to prove or exclude intrathecal production of HIV antibodies. By dilution, sera were adjusted to the IgG concentration of the corresponding CSF samples. Both samples were then serially diluted in log2 steps down to the detection limit and were tested in an anti-HIV ELISA. From the dilution obtained at the cut-off level, a quotient QHIV was derived as an indicator of intrathecal production of HIV antibodies. Six of a total of eight samples with a QHIV value of greater than or equal to 2 were correlated which the clinical diagnosis of AIDS-related dementia complex (ARDC). However, a QHIV less than 1 did not exclude the development of ARDC, as was shown during follow-up in one case. Different methods are compared for the determination of intrathecal production of IgG and anti-HIV. A quotient QHIV greater than or equal to 2 is suggested to be highly indicative of intrathecal production of anti-HIV as well as of the development of ARDC.

Progressive multifocal leukoencephalopathy: neurological findings and evaluation of magnetic resonance imaging and computed tomography.

On the basis of two of our cases we report here on the clinical symptoms and neuroradiological findings in patients with progressive multifocal leukoencephalopathy. Emphasis is put on the value of MRI in early stages of this disease, especially, and on the increased information provided by this method as compared to CT-scanning.

Conduction of electrically elicited impulses in peripheral nerves of diabetic patients.

Nerve conduction of single impulses and the ability to transmit frequent trains of stimuli were studied in sensory median and in sural nerves of controls and patients with diabetes mellitus. Decrease of relative amplitudes and increase of relative latencies were more marked in the diabetics as compared with normal controls when trains of stimuli were applied. An altered mode of the transmission of frequent trains could be demonstrated in 7 of 9 sural nerves and in 13 of 16 median nerves, which appeared to be normal when only a single stimulus was applied.

[Atypical facial neuralgia or depressive facial pain. Diagnostic aspects of a well-demarcated form of masked depression]. / "Atypische Gesichtsneuralgie" oder depressiver Gesichtsschmerz? Diagnostische Aspekte einer gut abgrenzbaren Form der larvierten Depression.

In three paradigmatical cases the problem of the diagnosis "atypical face pain" is discussed. On clinical inpatients can be demonstrated, that behind an "atypical face pain" a chronic depressive illness can be hidden. The symptom "facial pain" in these cases is part of an oligosymptomatic depressive disorder. A special antidepressant therapy is necessary in the clinical management of these "masked depressions". Therefore it is necessary to be reserved on diagnosing an "atypical face pain". The exact analysis of psychopathological disturbances can prevent these patients who in reality suffer from depressive face pain from therapies in maxillary surgery or in dentistry etc. that are far from useful.

[Cerebral refractory period of the somatosensory system in diseases of the central nervous system (author's transl)]. / Zerebrale Refraktärperiode des somatosensorischen Systems bei ausgewhlten Erkrankungen des Zentralnervensystems.

The duration of the refractory period of the somatosensory system was determined through the lengthening of latency respectively through the loss of Minimum 1 and Maximum 1; the median nerve was stimulated by single and double stimuli of variable interval, the somatosensory evoked potentials (SRAP) were averaged contralateral. The relative refractory time is independent of age, the absolute refractory time increased with advanced age. In genuine epilepsy with 3/s spike-waves the relative refractory period is shortened compared with the reference group of normal subjects. In multiple sclerosis the relative refractory time is distinctly increases in sign of demyelination on conduction in the central nervous system. The most distinct delays of refractory period are in cases with cerebrovascular disease and brain atrophy. The correlation between the clinical and neurophysiological results shows, that the single and double stimulation of the median nerve, combined with the analysis of the evoked potentials and the cerebral refractory period, is a good neurophysiologic cerebral function-test.

[Reversible alterations of peripheral nerve function in thyroid dysfunction (author's transl)]. / Reversible Funktionsstörungen peripherer Nerven bei Patienten mit Schilddrüsenerkrankungen.

In 7 patients with hyperthyroidism and 9 patients with hypothyroidism both thve before treatment and after a period of normal thyroid function of at least one year duration. As far as conduction velocity and relative refractory period are concerned there was no difference between hyperthyroid patients and normal persons, whereas in cases of hypothyroidism before treatment the conduction velocity was shown to be significantly reduced; moreover a prolonged relative refractory period and a decline in amplitude of the nerve action potential were found. These alterations of peripheral nerve function, interpreted as evidence of neuropathy, proved to be reversible when the thyroid function returned to normal.

Refractory period of human sural nerve action potential related to age in healthy probands.

150 sural nerves from 150 probands 10-70 years of age were investigated by applying supramaximal paired electric stimuli and recording the action potentials with needle electrodes. The responses to the first and second stimulus were evaluated with respect to latency and amplitude. Correlation of the electrophysiological findings with the age of the probands gave the following results: (1) Slight but statistical insignificant reduction of conduction velocity with advancing age up to 70 years. (2) Statistical significant decrease of amplitudes and prolongation of potential duration with advancing age. (3) No significant relationship between refractory period (latency and amplitude of the test response) and advancing age up to 70 years. The results are discussed in terms of their clinical meaning.

[Diplopia as an initial symptom of intracranial tumors]. / Diplopie als Initialsymptom bei intrakraniellen Tumoren.

Among 716 patients with intracranial blastomatous changes 74 showed diplopia as a consequence of involvement of the oculomotorius, trochlearis or (and) the abducens nerve. Diplopia as primary symptom of disease was observed in 20 cases. Patients with isolated initial diplopia were on average 10 years younger than patients where diplopia occurred only in the further course of the tumour. There were no preceding other diseases demonstrable in patients with initial diplopia. Papilloedema did not occur significantly more frequently in them than in patients with diplopia as secondary symptom. In rare cases latency between occurrence of diplopia and further symptoms may be months to two years. For this reason exact neurologic and ophthalmologic follow-up controls, particularly in young patients with isolated persistent diplopia, are required.

Sural nerve conduction velocity and refractory period in diabetics without clinical signs of neuropathy.

Twentysix patients aged 22-76 years with a duration of diabetes of 1 month to 23 years but without signs of symptoms of a peripheral nerve disease were studied. The nerve conduction velocity, the amplitude of the compound action potential and its restitution during the relative refractory period were examined in sural nerves. Nerve conduction velocity of the motor fibers were determined in the median, ulnar, tibial, and peroneal nerves. A reduced conduction velocity in motor nerves of the lower extremities were found in 10%, a reduced sensory nerve conduction velocity in 25%, and pathological changes of the refractory period in 50% of the patients. It is concluded that the determination of the relative refractory period can be used as a sensitive test in the early diagnosis of diabetic neuropathy.

[Somatosensory cortical evoked potentials in normal subjects to single and double median nerve stimulation (author's transl)]. / Somatosensorische Reizantwortpotentiale bei Normalpersonen nach Einzel- und Doppelstimulation des N. medianus.

On the wrist the median nerve of 42 normal subjects was stimulated by single and double stimuli and the contralateral cortical evoked potentials (SRAP) were evaluated with regard to peak-latencies, amplitudes and refractory period. SRAP after single nerve stimulations has 4-6 peaks in the first 100 ms, in 19 of 42 subjects there is an early peak ("peak 14-15") of the brain stem. The peak-latencies of minimum 1, maximum 1 and minimum 2 increase with the age not significantly. There are no right/left differences of the SRAP-amplitudes or -latencies. The duration of the relative refractory period was determined through the lengthening of latency respectively through the loss of minimum 1. The relative refractory time is independent of age, the absolute refractory time increase with advanced age. The refractory times of the first 4 peaks are not different for the right and left hemisphere. A slow alpha-rhythm correlate significantly with a higher absolute refractory time.

Cerebrovascular reserve capacity (CRC) in carotid artery disease: a routine test in selection for surgical treatment?

An increase of arterial carbon dioxide (CO2) partial pressure induces an increase of cerebral blood flow by dilatation of the resistance vessels. By the Transcranial Doppler sonographic technique (TCD) blood flow velocity as a correlate of flow volume can be measured within the great basal intracranial arteries. We investigated 8 patients with an internal carotid artery occlusion or high-grade stenosis and 5 cerebrovascular diseased patients without extracranial stenosis. 12 healthy volunteers and patients without vascular disease served as the control group. Blood flow velocities in the middle cerebral arteries were evaluated before and after 5 minutes of breathing a 5% CO2 gas mixture. In a prestudy the end tidal pCO2 was monitored during this procedure. As a result of the close parallelity of pCO2 increase in the prestudy group we planned to standardize the CO2 reactivity tests without consideration of the individual pCO2 values. The CO2 inhalation provoked a flow velocity increase of at least 20% in the control subjects (47.1 +/- 17.3%). The vascular diseased without extracranial stenosis responded with 34.8 +/- 17.4% (minimum: 23.5%, n. s.). The CO2 reactivity in cases of occlusion or greater than 50% stenosis was significantly decreased (p less than 0.001) both when considering only the affected sides (12.4 +/- 7.5%, maximum: 20%) and when including the non affected sides (22.6 +/- 15.0%). It is concluded that the CO2 reactivity test is a simple and valid method to evaluate the cerebrovascular reserve capacity in any case of uncertainty about the benefits of surgical treatment of a carotid stenosis. In future this technique might become one fundamental argument beside others in selecting adequate treatment.

[Diagnosis of primary non-Hodgkin lymphomas of the central nervous system]. / Zur Diagnostik primärer Non-Hodgkin-Lymphome des Zentralnervensystems.

In literature, primary malignant lymphomas (PML) of the central nervous system (CNS) have been known for many years under different names, although diagnosis was almost exclusively made via autopsy. It is only since the existence of computed tomography (CT) that there is a possibility of identifying or at least presuming intra vitam such malignancy and of securing the diagnosis via brain biopsy. This is most important because it enables an early treatment of patients by means of radiation and chemotherapy. We are documenting a new approach to identify the PML of CNS by four case histories of our own patients. This consists in the specific manner in which these tumours react to high doses of corticosteroid therapy. Under this treatment they diminish in size or even disappear completely. This can even be seen in other diseases, but when such behaviour of an intracerebral lesion is seen in a CT scan it should be of help in the evaluation of differential diagnosis and should be regarded as an important pointer towards achieving early diagnosis of PML of the CNS.