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Biomedical subjects

M Juhler

Publications and source records attributed to M Juhler.

At least 19 recordsLinked to original sources
PubMed2006

Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting.

OBJECTIVES: To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens. METHODS: In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes. RESULTS: One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation. CONCLUSIONS: A high prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer's disease.

Aged↗
PubMed2006

New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers.

Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells.

Adolescent↗
PubMed2005

Intraventricular or lumbar infusion test in adult communicating hydrocephalus? Practical consequences and clinical outcome of shunt operation.

BACKGROUND: To investigate the therapeutic consequences of restricting the CSF dynamic evaluation to a lumbar infusion test (LIT), as opposed to our formerly applied intraventricular assessment (VIT), in patients with communicating hydrocephalus (CH). METHOD: All patients over 18 years of age referred with clinical and radiological indication of treatment-requiring secondary CH (n = 50) or idiopathic normal-pressure hydrocephalus (INPH, n = 33) were subjected to a LIT. Subsequently, a combination of the results of the LIT (mainly the resistance to CSF outflow) and the clinical presentation determined whether to proceed with (a) VIT before a decision about shunt surgery, (b) shunt surgery or (c) no further diagnostic investigation or surgery. FINDINGS: In 88 percent of the patients with secondary CH and 80 percent of the patients with INPH the decision on shunt surgery was made after performing exclusively a LIT. The shunting success rate was 90 percent in patients with secondary CH and 82 percent in patients with INPH, which however in the latter group decreased to 76 percent, when including the patients undergoing an additional VIT. The achieved shunt success rates are equal or better, compared to the results from previous studies using intraventricular assessment. CONCLUSIONS: LIT and VIT are equally reliable for selecting shunt responsive patients with CH, using clinical improvement rate as the main criterion for comparison. The practical and economic consequences are substantial: the LIT can be performed in an outpatient setting, whereas VIT necessitates hospitalisation for 1-2 days including occupation of the neurosurgical theatre and postoperative neuro-intensive monitoring.

Adult↗
PubMed2001

Idiopathic normal-pressure hydrocephalus: evaluation and findings in a multidisciplinary memory clinic.

The diagnostic evaluation of patients with possible idiopathic normal-pressure hydrocephalus (INPH) is traditionally performed in the settings of either neurological, neurosurgical or psychiatric departments. The diagnostic procedure and findings in 71 consecutive patients referred with a clinical and radiological suspicion of INPH to our out-patient multidisciplinary memory clinic are evaluated. Primary diagnoses and potential concomitant disorders considered of secondary importance for the symptomatologies were established. Abnormal hydrodynamics, demonstrated by intraventricular pressure monitoring and infusion test were mandatory for the diagnosis of INPH. Mean age was 68 years and mean Mini-Mental State Examination (MMSE) score was 22. DSM IV criteria of dementia were fulfilled in 42%. In half of the referred patients (n=36), the suspicion of INPH was already disproved subsequently to the evaluation programme performed in the outpatient clinic. The main primary diagnosis was cerebrovascular disease (CVD) comprising 27% (n=19) of the referrals, whereas INPH was diagnosed in only 20% (n=14). Shunt improvement rate was 72%. The remaining patients were diagnosed as having one of 26 different conditions. A multiplicity of disorders mimics the INPH syndrome, with CVD being the primary differential diagnosis. Evaluating patients with possible INPH in an outpatient multidisciplinary memory clinic is an effective and rational diagnostic approach.

Adult↗
PubMed2001

Effects of alterations in arterial CO2 tension on cerebral blood flow during acute intracranial hypertension in rats.

Cerebrovascular reactivity to CO2 in clinical and experimental studies has been found to be impaired during increased intracranial pressure (ICP). However, from previous study results it has not been possible to estimate whether the impairment was caused by elevated ICP, or caused by decreased cerebral perfusion pressure (CPP). The current study was carried out in a group of unmanipulated control rats and in six investigation groups of six rats each: two groups with elevated ICP (30 and 50 mm Hg) and spontaneous arterial blood pressure (MABP), two groups with spontaneous ICP and arterial hypotension (77 and 64 mm Hg), and two groups with elevated ICP (30 and 50 mm Hg) and arterial hypertension (124 mm Hg). Intracranial hypertension was induced by continuous infusion of lactated Ringer's solution into the cisterna magna, arterial hypotension by controlled bleeding, and arterial hypertension by continuous administration of norepinephrine intravenously. Cerebral blood flow (CBF) was measured repetitively by the intraarterial 133Xe method at different levels of arterial PCO2. In each individual animal, CO2 reactivity was calculated from an exponential regression line obtained from the corresponding CBF/PaCO2 values. By plotting each individual value of CO2 reactivity against the corresponding CPP value from the seven investigation groups, CPP was significantly and directly related to CO2 reactivity of CBF (P < .001). No correlation was found by plotting CO2 reactivity values against the corresponding MABP values or the corresponding ICP values. Thus, the results show that CO2 reactivity is at least partially determined by CPP and that the impaired CO2 reactivity observed at intracranial hypertension and arterial hypotension may be caused by reduced CPP.

Analysis of Variance↗
PubMed2000

[Ischemic cerebral apoplexy in children].

During two years we identified eight children aged 1.5-10 years with cerebral ischaemic stroke. Prior to the stroke seven of eight children were in full health. Predisposing factors were endocarditis and trauma. Four children had prodomal symptoms prior to the infarction. All had acute hemiparesis on admission. Three of the children had fever, and five had varicellazoster infection three to 18 months prior to the stroke. Three children had convulsions. Seven of eight children had stenoses or occlusions of the middle cerebral or the basilar artery. Five children have persistent deficits and none have died. The children did not have coagulopathies, hypertension or arteriosclerosis. Echocardiography did not show patent foramen ovale. Early clinical and neuroradiological investigations are of importance in reaching the appropriate diagnosis.

Cerebral Hemorrhage↗
PubMed2000

Unusual clinical manifestations of disturbed CSF dynamics in hydrocephalic children.

OBJECTS: Clinical symptoms and signs of increased intracranial pressure (ICP) may be nonspecific and unreliable, or even entirely absent, in hydrocephalic infants and children. Even with a radiological examination, it is often difficult to distinguish between "arrested hydrocephalus" and slowly progressive hydrocephalus requiring treatment. METHODS: We present two cases with unusual and initially misleading clinical manifestations of increased ICP. In both cases, the disturbed cerebrospinal fluid (CSF) dynamics, i.e. raised ICP, were not recognised until demonstrated by a long-term ICP monitoring. In a 5-month-old boy with normal head circumference and normal psychomotor development, the sudden onset of episodes of torticollis and screaming were the only symptoms. No pathology underlying the developing hydrocephalus and the raised ICP could be established, but the boy's condition improved after a shunt operation. In the other case, symptoms and signs consisted primarily in a slowly progressive dilatation of the facial veins with onset at the age of 2-3 years. As the girl also presented a congenital subvalvular aortic stenosis, the venous congestion was initially thought to reflect a vena cava superior syndrome. Further radiological examinations, however, revealed an extensive sinus thrombosis underlying the raised ICP. The girl underwent shunt insertion, and the venous congestion was reduced. CONCLUSIONS: The cases illustrate that though clinical and radiological findings may be very doubtful, or unusual for increased ICP, direct diagnostic long-term ICP monitoring should always be contemplated. Only ICP monitoring can reveal with certainty whether disturbed CSF dynamics are involved, requiring a CSF diverting operation to treat and stabilise the condition.

Child, Preschool↗
PubMed2000

Effects of graded hyperventilation on cerebral blood flow autoregulation in experimental subarachnoid hemorrhage.

An impaired CBF autoregulation can be restored by hyperventilation at a PaCO2 level of about 2.9 to 4.1 kPa (22 to 31 mm Hg). However, it is uncertain whether the restoring effect can take place at lesser degrees of hypocapnia. In the current study, CBF autoregulation was studied at four PaCO2 levels: 5.33 kPa (40 mm Hg, normoventilation), 4.67 kPa (35 mm Hg, slight hyperventilation), 4.00 kPa (30 mm Hg, moderate hyperventilation), and 3.33 kPa (25 mm Hg, profound hyperventilation). At each PaCO2 level, eight rats 2 days after experimental subarachnoid hemorrhage (SAH) and eight sham-operated controls were studied. The CBF was measured by the intracarotid 133Xe method. The CBF autoregulation was found to be intact in all controls but completely disturbed in the normoventilated SAH rats. However, by slight hyperventilation, CBF autoregulation was restored in seven of eight SAH rats with a decline in CBF of 10%. The CBF autoregulation was found intact in all of the moderately or profoundly hyperventilated SAH rats, whereas the decline in CBF was 21% and 28%, respectively. In conclusion, hyperventilation to a PaCO2 level between 4.00 and 4.67 kPa (30 to 35 mm Hg) appears to be sufficient for reestablishing an impaired autoregulation after SAH.

Animals↗
PubMed1999

Indications for shunt insertion or III ventriculostomy in hydrocephalic children, guided by lumbar and intraventricular infusion tests.

The best therapeutic management for infantile hydrocephalus is not always obvious. Traditionally, shunt insertion has been performed when CSF dynamics have been considered abnormal. However, in cases of noncommunicating hydrocephalus endoscopic III ventriculostomy (ETV) has become a well-established treatment modality, but despite clinical and radiological information clinical improvement is not obtained in all cases. A reliable preoperative investigative procedure helping to select hydrocephalic children for ETV, shunt insertion or no operation, is urgently needed. We report three cases of infantile hydrocephalus, in which our operative management was guided by the results of cerebrospinal (CSF) infusion tests. With a lumbar infusion test we assessed the CSF resorption capacity, and thus whether shunting was indicated. Comparing the results with those of an intraventricular infusion test, we assessed the presence of any structural blockage of the CSF circulation between the ventricles and the subarachnoid compartment, which would indicate a possible effect of an ETV. Performance of both a lumbar infusion test and a subsequent intraventricular infusion test in hydrocephalic children seems to provide valuable information for the decision-making on surgery.

Cerebrospinal Fluid↗
PubMed1999

Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

Aged↗
PubMed1999

A multidisciplinary memory clinic in a neurological setting: diagnostic evaluation of 400 consecutive patients.

This report describes the operation of a multidisciplinary university hospital memory clinic in a neurological setting, and the diagnostic evaluations in 400 consecutive patients referred for cognitive symptoms and possible dementia during a period of 27 months (1 September 1995-31 December 1997). The mean age of the patients was 63.6 years (range 19-97). On clinical and neuropsychological examination, 46% of the patients fulfilled DSM IV criteria for dementia, 5% had selective amnesia, and 14% had other selective cognitive deficits. The remaining patients had either no significant cognitive deficits (31%) or were not evaluable (4%). A wide range of disorders from the fields of neurology, psychiatry, neurosurgery and internal medicine were identified as the underlying etiologies for the cognitive symptoms. Potentially reversible conditions were observed in 26% of the patients, not including the 11% in whom no specific underlying disease was identified. Concomitant conditions or risk factors with a potential influence on cognitive functions were identified in 61% of the patients. Diagnostic evaluation of patients with mild to moderate cognitive symptoms and possible dementia is an integrated multidisciplinary task, which should focus on the identification of non-progressive and potentially reversible etiologies, co-morbidity, selective cognitive deficits, and rare or atypical neurological conditions, as well as on the early identification of common progressive dementia disorders.

Adult↗
PubMed1999

Management of intrameatal vestibular schwannoma.

The growth of purely intrameatal vestibular schwannoma (VS) was investigated, in the period 1973-96 in a series of 40 patients with 40 unilateral VS. In the present study, the material was analysed and updated. By the end of the observation period (mean 3.6 years), 27 tumours (67.5%) revealed growth and 13 tumours (32%) had no measurable growth. Four growth patterns were observed: (A) 15 tumours (37.5%) exhibited constant growth; (B) 13 tumours (32.5%) had no measurable growth; (C) 8 tumours (20%) revealed growth subsequent to a no-growth period; and (D) 4 tumours (10%) showed different growth patterns during the observation period. The annual diameter growth rate ranged between 00 mm/year and 6.5 mm/year and the mean diameter growth per year was 3.2 mm. The findings of the present study, especially those for group B (the non-growing tumours) and C (tumour growth subsequent to a silent period) bring into question the reliability of the results achieved by radiosurgery, as without any intervention it may be that no tumour growth occurs.

Adolescent↗
PubMed1999

Effects of morphine on cerebral blood flow autoregulation CO2-reactivity in experimental subarachnoid hemorrhage.

Previous reports show that naloxone improves ischemic deficits and clinical conditions in patients after subarachnoid hemorrhage (SAH). These observations have raised concern about the routine use of morphine in the treatment of severe headache after SAH. The present study was carried out to investigate the effects of morphine on cerebral vasoreactivity after experimental SAH. Cerebral blood flow (CBF) autoregulation was studied in two groups of eight rats each with experimental SAH. A bolus intravenous injection of morphine, 1 mg/kg, was administered in one group and the other was used as a control group. During eucapnia, CBF was measured by the intracarotid 133Xenon method during decreasing mean arterial blood pressure (MABP). CO2-reactivity was investigated in two corresponding groups where CBF was measured at decreasing PaCO2 levels during constant MABP. Morphine decreased mean baseline CBF by 34% and 26% in the study of autoregulation and CO2-reactivity, respectively. Cerebral blood flow autoregulation was found impaired in both controls and the morphine group. However, the mean slope of the linear regression lines of CBF/MABP was 0.49 +/- 0.32 ml/100g/min/mm Hg in the morphine group, which was significantly lower than 1.24 +/- 0.59 ml/100g/min/mm Hg in the controls (p < 0.05). Also the mean CO2-reactivity was significantly lower, 0.64 +/- 0.53 %/0.1kPa, in the morphine group, compared to 2.36 +/- 0.87 %/0.1kPa in the controls (p < 0.001). The results show that in rats with SAH, morphine partially restores CBF autoregulation but attenuates CO2-reactivity.

Animals↗
PubMed1998

Novel pharmacologic strategies in the treatment of experimental traumatic brain injury: 1998.

The mechanisms underlying secondary or delayed cell death following traumatic brain injury are poorly understood. Recent evidence from experimental models suggests that widespread neuronal loss is progressive and continues in selectively vulnerable brain regions for months to years after the initial insult. The mechanisms underlying delayed cell death are believed to result, in part, from the release or activation of endogenous "autodestructive" pathways induced by the traumatic injury. The development of sophisticated neurochemical, histopathological and molecular techniques to study animal models of TBI have enabled researchers to begin to explore the cellular and genomic pathways that mediate cell damage and death. This new knowledge has stimulated the development of novel therapeutic agents designed to modify gene expression, synthesis, release, receptor or functional activity of these pathological factors with subsequent attenuation of cellular damage and improvement in behavioral function. This article represents a compendium of recent studies suggesting that modification of post-traumatic neurochemical and cellular events with targeted pharmacotherapy can promote functional recovery following traumatic injury to the central nervous system.

Animals↗
PubMed1998

The upper limit of cerebral blood flow autoregulation in acute intracranial hypertension.

The present series of experiments was performed to investigate the influence of acute intracranial hypertension on the upper limit (UL) of cerebral blood flow (CBF) autoregulation. Three groups of eight rats each--one with normal intracranial pressure (ICP) (2 mmHg), one with ICP = 30 mmHg, and one with ICP = 50 mmHg--were investigated. Intracranial hypertension was maintained by continuous infusion of lactated Ringer's solution into the cisterna magna, where the pressure was used as ICP. Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure (MABP)-ICP, was increased stepwise by continuous intravenous infusion of norepinephrine. CBF was calculated by the intracarotid 133Xe method. In all three groups the corresponding CBF/CPP curve included a plateau where CBF was independent of changes in CPP, showing intact autoregulation. At normal ICP the UL was found at a CPP of 141 +/-2 mmHg, at ICP = 30 mmHg the UL was 103+/-5 mmHg, and at ICP = 50 mmHg the UL was found at 88+/-7 mmHg. This shift of the UL was more pronounced than the shift of the lower limit (LL) of the CBF autoregulation found previously. We conclude that intracranial hypertension is followed by both a shift toward lower CPP values and a narrowing of the autoregulated interval between the LL and the UL.

Animals↗