Biomedical subjects

H M Mehdorn

Publications and source records attributed to H M Mehdorn.

At least 19 recordsLinked to original sources

PubMed2006

Induction of immediate early gene expression by high-frequency stimulation of the subthalamic nucleus in rats.

Deep brain stimulation is associated with delayed improvement of parkinsonian symptoms, such as hypokinesia with subthalamic nucleus stimulation, or dystonia with globus pallidus internus stimulation. The latency observed is better explained by molecular alterations than immediate electrophysiological processes, and clinical improvement may involve adaptive gene expression. Here, we have studied immediate early gene expression as fast molecular response to subthalamic nucleus stimulation. Bipolar electrodes were implanted bilaterally into the subthalamic nucleus of anesthetized male Wistar rats. High-frequency stimulation (130 Hz or 80 Hz, 60 micros, 300 microA) or low-frequency stimulation (5 Hz, 60 micros, 300 microA) was performed with the right electrode for 15, 60, 120, and 240 min whereas the silent left electrode served as negative control. Brains were fixed by transcardial perfusion and frozen sections were stained with polyclonal antibodies directed against three immediate early gene-encoded proteins, c-Fos, c-Jun, and Krox-24 (NGFI-A, Egr-1, Zif268, Tis8, Zenk). After 120 and 240 h, c-Fos immunoreactivity was strongly upregulated in subthalamic nucleus neurons on the stimulated site. In contrast, no c-Fos immunoreactivity was detected on the non-stimulated site except for single positive cells located in close proximity to the electrode tracks. Furthermore, c-Fos immunoreactivity was induced in subthalamic nucleus projection areas, such as primary and secondary motor cortex, primary somatosensory and insular cortex, lateral and medial globus pallidus, suprageniculate thalamic nucleus, pontine nuclei, medial geniculate nucleus, and substantia nigra. Similarly, c-Jun and Krox-24 were induced at the site of stimulation and in projection areas following high-frequency subthalamic nucleus stimulation. Whereas high frequency stimulation with 80 Hz was similarly effective none of the three immediate early gene-encoded proteins was induced with low-frequency stimulation (5 Hz) for 4 h. This is in accordance with the therapeutic effects of deep brain stimulation which are only elicited with high frequency stimulation. Our data provide evidence that immediate early gene expression in the subthalamic nucleus is rapidly and substantially induced by high-frequency stimulation. The induction of immediate early genes in projection sites suggests ipsilateral transsynaptic modulation of neuronal activity.

Animals↗

PubMed2005

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Action Potentials↗

PubMed2005

Unusual locations for cavernous hemangiomas: report of two cases and review of the literature.

Cavernous hemangiomas are most commonly found within the subcortical neural parenchyma near the fissura Rolandi, in the basal ganglia, or in the brain stem. Because of advancing neuro-imaging technology and thus resulting in a higher incidence of cavernous hemangiomas they have rising impact in neurosurgery. We present two unusual cases of extra-axial cavernous hemangiomas: one located at the frontal falx, the other within the bone of the right frontal bone. We discuss these and other cases in the literature with respect to the more common differential diagnoses and the appropriate therapy regimen for cavernous hemangiomas in these locations.

Adult↗

PubMed2005

Deep brain stimulation for idiopathic or secondary movement disorders.

Deep brain stimulation has gained increasing interest in the treatment of movement disorders. Presenting our clinical series of 179 patients operated upon since 1999, the indications, risks and benefits for the patients are discussed in order to further improve the techniques and their applications.

Deep Brain Stimulation↗

PubMed2005

Treatment options and results in cervical myelopathy.

Cervical myelopathy is a clinical entity resulting from external compression of the cervical medulla. The clinical course can be divided into the acute form (secondary to trauma) versus subacute (progression within weeks to months) and chronic cervical myelopathy (months to years). The clinical picture of myelopathy is that of unsteady gait with long-tract signs, such as hyperreflexia, spasticity and extensor plantar responses. Between 1997 and 2000, 359 consecutive patients have been operated on in our department presenting with a variety of symptoms related to compression of the cervical medulla. Beside of standard MRI for all patients we applied SSEPs, gait analysis and dynamic MRI studies as additional helpful tools in evaluating selected patients pre- and postoperatively. We prefer the anterior approach as first-line approach because in the majority of patients the osteophytic spurs are more dominant anteriorly, and after anterior decompression and stabilization the posterior approach appears safer. We also favor the more extended approach of spondylectomy versus multilevel decompression in patients with bisegmental or multisegmental spinal canal stenosis. However it seems to be that radicular decompression is better achieved through multilevel decompression than through spondylectomy.

Decompression, Surgical↗

PubMed2005

Metastatic meningioma WHO grade II of the cervical spine: case report and review of the literature.

The authors report a rare case of metastatic atypical meningioma WHO grade II involving the dorso-lateral region of the cervical spine and causing spinal cord compression in a 76-year-old man. The patient was treated surgically in June 1998 for an atypical parasagittal meningioma in the right frontal lobe. Local recurrence with extension to the left hemisphere required surgical treatment in January 2000, and in December 2000 recurrence caused paraplegia of the lower extremities and paresis of the left arm. A 3 (rd) operation was carried out in January 2001, followed by radiotherapy with a total dose of 45 Gy. The patient presented again in March 2003 because of pain in the neck and a progredient new paresis and paresthesia of the right arm. Computed tomogram of the cervical spine showed a large tumor with compression of the spinal cord. MRI was not possible due to a pacemaker which had been implanted in the meantime. Surgical subtotal removal of the tumor via hemilaminectomy of the 3 (rd) and 4 (th) cervical vertebrae was performed. After decompression of the cervical spine the paresis of the right arm improved, the paraplegia of the legs and the left arm, existing since December 2000, remained unchanged. Histological findings of the cranial lesions and the metastatic lesion had a similar appearance and were compatible with atypical meningioma (WHO grade II).

Aged↗

PubMed2004

[Benign fibro-osseous tumors of the frontal skull base with intracranial extension. Report of 2 cases].

We report on two patients with ossifying fibroma of the anterior skull base with intracranial extension. A psammomatoid ossifying fibroma was removed from a 29 year old female patient, and in a 37 year old female patient a cemento ossifying fibroma was removed. The main clinical symptom in both cases was headache. Surgery took place after diagnosis and therapy in an interdisciplinary operation with ENT colleagues. The ossifying fibroma is a benign neoplasm mainly affecting the maxilla and mandible. Complete removal is better than a curettage of the tumor.

Adult↗

PubMed2004

Pattern of recurrence following local chemotherapy with biodegradable carmustine (BCNU) implants in patients with glioblastoma.

OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. A local chemotherapy applied directly to the resection cavity may act directly on residual tumor cells in adjacent brain possibly leading to a local control of the tumor and increased survival. METHODS: We have analyzed the pattern of recurrence using serial MRI studies of 24 patients treated with GLIADEL Wafers or placebo wafers following resection of glioblastomas. RESULTS: Of 24 patients 11 received carmustine wafers and 13 placebo. The age distribution and Karnowsky performance scores of the two populations were not different. However, the median survival (14.7 versus 9.5 months; P = 0.007) and the time to neurological deterioration (12.9 +/- 4.85 vs. 9.4 +/- 2.73 months; P = 0.035) was significantly longer in the treatment group versus the placebo treated control. Preoperative and follow up MRI studies were evaluated in a blinded fashion. Out of 24 patients that entered the analysis 11 showed clearance of all contrast enhancement following resection of glioblastomas. Seventeen tumors progressed locally and 7 showed different patterns of distant failure. Within the carmustine treated group 8 patients showed a local treatment failure with recurrent tumors immediately adjacent to the resection cavity or progression form a residual tumor. Three patients showed a multifocal distant and local pattern of failure after complete or subtotal removal. In no case the local chemotherapy resulted in a distant recurrence only. However, the time to radiographic progression was 165.1 +/- 80.75 days for the GLIADEL Wafer group and 101.9 +/- 43.06 days for the placebo group (P = 0.023). CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time. Local chemotherapy with carmustine containing wafer implants did not result in an altered pattern of recurrence and did not promote multifocal patterns of recurrence.

Absorbable Implants↗

PubMed2004

Primary peripheral T-cell lymphoma of the central nervous system.

UNLABELLED: A 47-year-old man was admitted to our hospital with a nine-week history of visual disturbance, headache, disorientation and facial nerve palsy. Serial cranial magnetic resonance imaging (MRI) revealed progressive bilateral occipital edema with hemorrhage and meningeal involvement. There were no hints of hereditary or acquired immunodeficiency. Laboratory examination for bacterial and viral causes was negative. Open brain biopsy revealed primary central nervous system lymphoma of the extraordinary rare so-called "peripheral" T-cell type. The further course was fatal; the patient died 10 weeks after the onset of symptoms from tumor progression before planned chemotherapy could be started. CONCLUSION: If primary central nervous system lymphoma (PCNSL) is suspected, brain biopsy -- either open biopsy or stereotactic biopsy -- should be performed straight away to enable a rapid start of chemotherapy and/or radiotherapy. Peripheral T-cell lymphoma was highly aggressive in this case leading to the patient's death within several weeks.

Biopsy↗

PubMed2004

Evidence for distinct cognitive deficits after focal cerebellar lesions.

OBJECTIVES: Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. METHODS: We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. RESULTS: Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. CONCLUSIONS: Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought."

Adult↗

PubMed2004

Study of clinical features of amyloid angiopathy hemorrhage and hypertensive intracerebral hemorrhage.

OBJECTIVE: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. METHODS: From June 1994 to Oct., 2000, 83 patients admitted to our service with acute intracerebral hemorrhage (ICH) were investigated retrospectively; 41 patients with histologically proven diagnosis of cerebral amyloid angiography and 42 patients with clear history of hypertension were investigated. RESULTS: Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74.0 years vs 66.5 years, P < 0.05). There was a significantly higher number of hematomas > or = 30 ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglional hemorrhage was seen in CAA, but in 40.5% in HTN. In CAA-related ICH, subarachnoid hemorrhage (SAH) was seen in 26 patients (63.4%) compared to only 11 patients (26.2%) in HTN-related ICH. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Typical features of CAA-related ICH included lobar distribution affecting mainly the lobar superficial areas, lobulated appearance, rupture into the subarachnoid space, and secondary IVH from the lobar hemorrhage. More specifically, multiplicity of hemorrhage, bilaterality, and repeated episodes also strongly suggest the diagnosis of CAA. Multiple hemorrhages, defined as 2 or more separate hematomas in multiple lobes, accounted for 17.1% in CAA-related ICH. CONCLUSION: There are certain features in CAA on CT and MRI and in clinical settings. To some extent, these features may contribute to distinguishing CAA from HTN related ICH.

Adult↗

PubMed2003

Dysplastic gangliocytoma of the cerebellum: rare differential diagnosis in space occupying lesions of the posterior fossa.

Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos) is a rare space occupying lesion of the posterior fossa with some typical neuroradiological features which can be better diagnosed in the MRI era. This is the major CNS manifestation of Cowden disease. In recent years more publications underlined the association of these hamartomatous lesions. We add another patient with a dysplastic gangliocytoma of the cerebellum who also had a thyroid adenoma and fulfilled the criteria of having Cowden disease.A problem of surgical removal of these tumors is missing the borderline between tumor and healthy cerebellum tissue so that incomplete removal of the tumor is not rare. Surgical removal of these tumors in an open MRI unit would be a good indication.

Adult↗

PubMed2003

Subarachnoid hemorrhage of unknown origin and the basilar artery configuration.

It is unclear whether the configuration of the basilar artery (BA) in patients with subarachnoid hemorrhage (SAH) of unknown origin is comparable to that in normal subjects or whether there are differences which may help to identify the origin. We studied the BA configuration in 57 patients with SAH of unknown origin (10%), who were identified in a prospectively collected series of 549 SAH patients consecutively admitted to our service over a 9-year period. There were 30 patients (53%) with non-perimesencephalic SAH and 27 with perimesencephalic SAH (47%). According to a standardized algorithm we determined, on straight anteroposterior digital subtraction angiography (DSA), the width of the proximal BA segment at the origin of the anterior inferior cerebellar artery and the width of the most distal BA segment between the superior cerebellar arteries and the posterior cerebral arteries. Based on these measurements we calculated the distal-proximal BA ratios and compared them to the ratios obtained in a control group of 31 patients who had DSA for reasons other than aneurysmal SAH. The mean ratio in patients with non-perimesencephalic SAH of unknown origin was 1.150 (range: 1.080-1.230). In patients with perimesencephalic SAH of unknown origin it was 1.156 (range: 1.120-1.250). In the control group the mean ratio was 1.163 (range: 1.125-1.200). There are no variations in the configurations of the BA which could possibly explain the cause of this type of SAH or clarify the origin of hemorrhage.

Adult↗

PubMed2003

Age-related expression of p53, Mdm2, EGFR and Msh2 in glioblastoma multiforme.

OBJECTIVE: Glioblastoma multiforme (GBM) is a major cause of morbidity and mortality in neurosurgical patients. Despite the overall poor prognosis a range in survival times exists. Many approaches have been undertaken to define patient subgroups based on molecular changes. The aim of this study was to assess a possible correlation between the immunohistochemical p53, Mdm2, EGFR and Msh2 expression and age. METHOD: 143 patients (77 male, 66 female) were included in this retrospective study who underwent craniotomy for newly-diagnosed GBM between May 1994 and February 2000. For statistical analysis, patients were separated into three age groups: 1. < 40 years, 2. 40-60 years, 3. > 60 years. Immunohistochemical staining (IHC) was performed using anti-p53 (clone DO-1), anti-Mdm2 (clone IF-2), anti-EGFR (clone H11) and anti-Msh2 antibodies (clone AB-1). The results were compared with the Ki67/MIB-1 proliferation index (Ki67 PI) and patient survival. FINDINGS: P53 protein expression was significantly decreasing with advanced age (p < 0.05) whereas EGFR and Mdm2 expression was increasing (p < 0.05; p=0.01). Msh2 expression was unrelated to age. Multivariate analysis revealed Msh2 protein expression as a significant predictor of prolonged survival (p=0.004) whereas p53, Mdm2 and EGFR were not associated with patient survival. P53, Mdm2, EGFR and Msh2 expression was not associated with the Ki67 PI. INTERPRETATION: Our results support the hypothesis that in GBM patients a complex relationship exists between the p53, Mdm2 and EGFR expression and age. Msh2 expression is not related to age. Notably, nuclear Msh2 expression turned out to be an independent prognostic indicator.

Adolescent↗

PubMed2003

p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme.

BACKGROUND: The clinical course of glioblastoma multiforme is characterised by invasive growth and regular recurrence. Many genetic alteration have been identified in the genesis of the disease. However, information about immunohistochemical expression in recurrent lesions is sparse. OBJECTIVES: To determine (1) whether the p53/mdm2/EGFR/msh2 expression pattern differs in initial v recurrent glioblastoma multiforme; (2) whether a possible change in expression correlates with prognostic variables (progression-free survival time, total survival time); and (3) whether chemotherapy in addition to surgery and radiotherapy influences the p53/mdm2/EGFR/msh2 expression profile. METHODS: 27 patients were studied. They met the following criteria: histologically confirmed diagnosis of glioblastoma multiforme (WHO IV); total tumour resection at initial craniotomy; at least one re-craniotomy for glioblastoma multiforme recurrence; age 21 years or older. All underwent radiotherapy of at least 54 Gy, and 17 received additional chemotherapy. Immunohistochemical staining of initial tumours and recurrences was done with the following monoclonal antibodies: anti-p53 (DO-1), anti-mdm2 (IF-2), anti-EGFR (H11), and anti-msh2 (AB-1). RESULTS: In comparison with the initial tumour, recurrent lesions were characterised by reduced expression of p53 (p < 0.0001) and msh2 (p = 0.0012), while the numbers of mdm2 (p = 0.02), EGFR (p < 0.0001), and msh2 positive specimens (p < 0.0001) were reduced. Chemotherapy was associated with reduced msh2 expression (p < 0.0001). Immunohistochemical variables were not associated with patient survival. CONCLUSIONS: There are significant differences in the p53/mdm2/EGFR/msh2 expression patterns in initial v recurrent glioblastoma multiforme. There may be interactions between chemotherapy and changes in the msh2 expression.

Adult↗

PubMed2003

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Aged↗

PubMed2003

Cerebral vasomotor reactivity testing in head injury: the link between pressure and flow.

BACKGROUND: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity in patients with head injury. OBJECTIVES: To validate this index and study its relation with cerebral blood flow velocity and cerebral autoregulation; and to identify variables associated with impairment or preservation of cerebral vasomotor reactivity. METHODS: The PRx was validated in a prospective study of 40 head injured patients. A PRx value of less than 0.3 indicates intact cerebral vasomotor reactivity, and a value of more than 0.3, impaired reactivity. Arterial blood pressure, intracranial pressure, mean cerebral perfusion pressure, and cerebral blood flow velocity, measured bilaterally with transcranial Doppler ultrasound, were recorded. Dynamic cerebrovascular autoregulation was measured using a moving correlation coefficient between arterial blood pressure and cerebral blood flow velocity, the Mx, for each cerebral hemisphere. All variables were compared in patients with intact and impaired cerebral vasomotor reactivity. RESULTS: No correlation between arterial blood pressure or cerebral perfusion pressure and cerebral blood flow velocity was seen in 19 patients with intact cerebral vasomotor reactivity. In contrast, the correlation between these variables was significant in 21 patients with impaired cerebral vasomotor reactivity, whose cerebral autoregulation was reduced. There was no correlation with intracranial pressure, arterial blood pressure, cerebral perfusion pressure, or interhemispheric cerebral autoregulation differences, but the values for these indices were largely within normal limits. CONCLUSIONS: The PRx is valid for monitoring and quantifying cerebral vasomotor reactivity in patients with head injury. This intracranial pressure based index reflects changes in cerebral blood flow and cerebral autoregulatory capacity, suggesting a close link between blood flow and intracranial pressure in head injured patients. This explains why increases in arterial blood pressure and cerebral perfusion pressure may be useful for reducing intracranial pressure in selected head injured patients (those with intact cerebral vasomotor reactivity).

Adolescent↗

PubMed2003

Subthalamic nucleus stimulation in Parkinson's disease: correlation of active electrode contacts with intraoperative microrecordings.

BACKGROUND/AIMS: The most effective site for subthalamic nucleus (STN) stimulation has remained unclear. The position of active contacts relative to the dorsal margin of the STN was determined. METHODS: Electrodes (n = 49) were implanted following STN mapping by microrecording and microstimulation along five tracks (n = 25 patients). The stereotactic position of active contacts was determined and correlated with microrecordings using an algorithm for direct three-dimensional comparisons (n = 37). RESULTS: Most active contacts were detected within +/-1.0 mm from the dorsal margin of the STN as defined by microrecording (32.4%) or farther dorsal in the subthalamic area (37.8%), and only 29.7% were localized to the STN proper. This was consistent with the average stereotactic coordinates of the active contacts in these three groups. CONCLUSION: Our data suggest that the dorsal border area of the STN is the most effective target. Besides the dorsolateral STN (sensorimotor part) this may include projections from/to STN, the zona incerta, and pallidofugal projections in the fields of Forel.

Electric Stimulation Therapy↗