PubMed Health⌕ Search

Biomedical subjects

F C Dohan

Publications and source records attributed to F C Dohan.

At least 19 recordsLinked to original sources
PubMed1999

Synaptophysin immunoreactivity in temporal lobe epilepsy-associated hippocampal sclerosis.

We have previously devised a semiquantitative grading system for hippocampal sclerosis (HS) in specimens resected for intractable temporal lobe epilepsy. The grades range from zero to four based on the amount and distribution of neuronal loss and gliosis. In the present study hippocampal sections from 25 patients who had temporal lobe epilepsy and had previously been assigned a grade were examined with synaptophysin immunohistochemistry, and the synaptic content in specific hippocampal fields was correlated with the results of the HS grading system. There was evidence of both significant synaptic loss and increased synaptic density in different fields of the hippocampus with increasing HS. A marked decrement of synaptic inmmunostaining was present in fields CA1 and CA4 that were highly correlated with HS grade. Sector CA4 seemed to respond in a more graded or continuous way to the pathological insults occurring in temporal lobe epilepsy than did CA1, which appeared to exhibit an all or nothing response. Also, while the width of the outer part of the molecular layer of the dentate (mid) gyrus decreased with increasing HS grade, the inner part of the mid became wider and showed an increased synaptic density so that the overall width of the mid was increased in the high-grade group. We conclude that quantitative measurement of synaptic loss in CAI and CA4 using synaptophysin immunohistochemistry is a sensitive method for detecting HS and correlates well with the empirically derived HS grading scale, with CA4 exhibiting a more graded response than CA1. In addition, a plasticity response in the inner part of the mld in patients with high-grade HS has been confirmed and quantitated.

Adult↗
PubMed1999

Prediction of presence of hippocampal sclerosis from intracarotid amobarbital procedure memory asymmetry scores and epilepsy on set age.

Identification of the pathological status of the hippocampus prior to surgery is important since the absence of hippocampal sclerosis (HS) carries risks to memory function following anterior temporal lobectomy (ATL). We studied 62 patients undergoing ATL (31 L, 31 R) for intractable epilepsy of temporal lobe origin in whom no pathology was identified apart from HS. An intracarotid amobarbital procedure (IAP) was performed as part of the preoperative evaluation. All patients were left hemisphere dominant for language. IAP memory testing was according to the protocol of Loring. We examined IAP memory asymmetry scores at four levels of difference (<2, > or =2, > or =4, > or =6) as a function of the presence (HS+) or absence (HS-) of HS. A logistic regression analysis was performed with HS+ as the dependent variable, and age at onset of epilepsy, age at time of surgery, gender, side of surgery and significant IAP memory asymmetry as independent variables. At each level of memory asymmetry, onset age and memory asymmetry were the only predictors of HS+. Younger age at onset was associated with HS+. Curves were constructed showing probability of HS+ for age at onset for each level of asymmetry. These can be used to predict the likelihood of presence of HS based on age at onset of epilepsy and the IAP memory asymmetry score. It is concluded that IAP memory asymmetry scores reflect the functional and pathological status of the hippocampus, and greater asymmetry increases the probability of finding HS in the resected hippocampus.

Adult↗
PubMed1998

Synaptophysin immunohistochemistry densitometry measurement in resected human hippocampus: implication for the etiology of hippocampal sclerosis.

Synaptophysin (SY) is a protein expressed at presynaptic vesicles. SY immunohistochemistry (IHC) was undertaken in surgically resected hippocampal specimens from 25 patients with intractable epilepsy. All were investigated with chronic ictal EEG videotelemetry, which showed a temporal onset in each case, and all had normal magnetic resonance imaging (MRI). The density of reaction product of SY IHC was used to generate optical density (OD) measurements as an estimate of synaptic density in CA1 and CA4 fields (ODCA1 and ODCA4), and inner third and outer two-thirds of the molecular layer of the dentate gyrus (ODIML and ODOML). There was significant correlation between ODCA1 (r=0.619, P=0.001) and ODCA4 (r=0.639, P=0.001) and onset age of epilepsy. There was no correlation between ODCA1 and duration of epilepsy. There was correlation between ODCA4 and duration (r=-0.412, P=0.041), but partial correlations showed no significant correlation between ODCA4 and duration when controlling for onset, although correlation between ODCA4 and onset when controlling for duration remained significant (r=0.536, P < 0.01). Univariate ANOVA revealed onset age to be the only predictor of ODCA1 and ODCA4. Chronological age and duration were not predictors. There was no correlation between ODIML or ODOML and either onset age or duration. ODIML and ODOML were not predicted by onset age, duration or chronological age. These findings support the hypothesis that the major cause of hippocampal sclerosis is an age specific insult rather than the result of repeated seizures.

Adult↗
PubMed1998

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression-based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed.

Adult↗
PubMed1998

Naming decline after left anterior temporal lobectomy correlates with pathological status of resected hippocampus.

PURPOSE: To evaluate the determinants of postoperative change in visual confrontation naming ability and the differential sensitivity of two common tests of confrontation naming. METHODS: In a group of 99 patients undergoing lobectomy of the left, language-dominant anterior temporal lobe, we examined naming ability using two measures: the 60 item Boston Naming Test (BNT), and the Visual Naming (VN) subtest of the Multilingual Aphasia Examination (MAE). ATL entailed resection of lateral temporal lobe followed by microsurgical complete removal of hippocampus. Language mapping was not performed. The status of the resected hippocampus was graded on a scale 0-4 of hippocampal sclerosis (HS). A dichotomous grouping HS- (grades 0 and 1, n = 34) and HS+ (grades 3 and 4, n = 61) was effected. Age at surgery, age of epilepsy onset, sex, extent of lateral temporal resection, Full-Scale IQ (FSIQ), and preoperative naming scores were also examined as potential predictors of pre- versus postoperative naming change. RESULTS: Preoperative BNT and VN scores were significantly worse for HS+ than for HS- (BNT, p < 0.05; VN, p = 0.001). Postoperatively, BNT and VN scores significantly declined for HS- as compared with HS+ patients (p < 0.001). For individual risk, the 90th centile of reliable change index (RCI) was used. By this criterion, of the total sample, 39% evidenced decline on the BNT and 17% evidenced decline on the VN. Logistic regression analysis with backward elimination showed HS to be the only predictor of decline in BNT and HS and sex to be the only predictors of VN decline. Males were more at risk than females. Age, age at onset, extent of lateral resection, preoperative scores, and FSIQ were not predictors. Using age at onset as a proxy for HS+/HS- we calculated probabilities for naming decline for given onset age. CONCLUSIONS: Both preoperative and postoperative change in naming ability are associated with the pathological status of the hippocampus. The potential interpretations and implications of these findings are discussed.

Adult↗
PubMed1998

Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor.

OBJECT: Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen++ +-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). METHODS: The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 micromol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 micromol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 micromol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-micromol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 micromol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. CONCLUSIONS: This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

Analysis of Variance↗
PubMed1997

Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L).

STUDY DESIGN: A canine lumbar laminotomy and discectomy model was used to evaluate the effects of a resorbable gel, ADCON-L (Gliatech Inc., Cleveland, OH), in reducing peridural scar formation and to assess the healing progress of immediately adjacent normal structures. OBJECTIVES: To compare peridural scar formation and anulus fibrosis healing with and without the use of ADCON-L in an animal model that closely replicates the common human surgical procedure. SUMMARY OF BACKGROUND DATA: ADCON-L has been shown to reduce the development of peridural scars in rat, rabbit, and canine laminectomy models in previous investigations; discectomies were not performed in these previous studies, however, and thus anular healing could not be assessed. METHODS: Seven adult mongrel dogs underwent a three-level unilateral lumbar hemilaminotomy and anular fenestration. In each dog, the ADCON-L was applied to two randomly assigned sites around the discectomy, the nerve roots, and the hemilaminotomy. The third site underwent surgery, but was left untreated (sham surgery only). The canines were killed 8 weeks after surgery, and a gross anatomic assessment of scar formation was done using microdissection by an observer blinded to treatment. A numerical rating system was developed to assess the relative amount and tenacity of the anterior scarring (discectomy site) and posterior scarring (hemilaminotomy site). The healing of the anular defect was assessed histologically. RESULTS: ADCON-L significantly reduced peridural fibrosis in this lumbar discectomy model compared with the sham treated sites (p < 0.05). Further, the superficial layers, the posterior longitudinal ligament, and the anulus fibrosus healed well in the ADCON-L treated sites. CONCLUSIONS: ADCON-L reduced local peridural fibrosis after lumbar laminotomy and discectomy without impacting the healing of the surrounding tissues.

Animals↗
PubMed1997

Reorganization of verbal memory function in early onset left temporal lobe epilepsy.

The purpose of this investigation was to examine the issue of reorganization of verbal memory function following early insult to the left mesial temporal region. It was hypothesized that reorganization of memory function was most likely to occur in those patients with an early age of seizure onset who have a more limited degree of extra-hippocampal neuropathology. Fifty-four patients with epilepsy of unequivocal left temporal lobe origin were classified into four groups on the basis of the presence/absence of hippocampal sclerosis and degree of postoperative seizure relief. Measures of verbal learning and memory as well as nonmemory measures were administered both before and 6 to 8 months after anterior temporal lobectomy. Findings were consistent with the reorganization proposal. The clinical and theoretical significance of the findings are discussed.

Adult↗
PubMed1996

Cervical kyphosis after resolution of myopathic head drop. A case report.

STUDY DESIGN: This is a case report. OBJECTIVES: To present a case of cervical kyphosis after resolution of myopathic head drop. SUMMARY OF BACKGROUND DATA: Myopathic head drop is a severe and persistent local myopathy that never progresses beyond the neck extensor muscles. METHODS: A case is reported of a hospitalized psychiatric patient who experienced the sudden onset of severe neck extensor weakness consistent with myopathic head drop. RESULTS: Although myopathic head drop resolved after 2 years, it left a disabling residual skeletal deformity of the cervical spine. CONCLUSIONS: Myopathic head drop may be a cause of cervical kyphosis.

Adaptation, Physiological↗
PubMed1996

Solitary focal demyelination in the brain as a paraneoplastic disorder.

Solitary focal demyelination (SFD) in the brain is an uncommon and poorly understood disorder of uncertain etiology that may represent an intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis. In a few reported cases of SFD, the patient was briefly noted to have a nonneurological malignancy. We studied two patients who had solitary focal lesions in the brain. Utilizing magnetic resonance imaging and tissue biopsy, we found the characteristics of the brain lesions in these two patients to be those of SFD. In our combined experience over the past 10 years, we have encountered no similar brain lesions at our medical center. We found it remarkable that both of these patients also had malignancy outside of the nervous system. One had a seminoma, and the other a lymphoma. We conclude that some cases of SFD in the brain may occur as a paraneoplastic disorder associated with nonneurological malignancies.

Adult↗
PubMed1996

Hippocampal sclerosis and verbal encoding ability following anterior temporal lobectomy.

Previous research has shown that the degree of verbal memory decline following left anterior temporal lobectomy (ATL) is inversely related to the extent of neuronal dropout in resected left hippocampus. The goal of this investigation was to clarify further the nature of the free recall impairment and to determine the relative contribution of verbal retrieval and encoding processes. Seventy-six patients who underwent left (n = 46) or right (n = 30) ATL were classified according to the presence or absence of hippocampal sclerosis and pre- to postoperative changes in free recall, cued recall and recognition memory for verbal material were examined. Surgically induced free recall impairments were selectively associated with resection of nonsclerotic left hippocampus and represented a 29-35% decline in verbal learning ability. These free recall deficits were due to postoperative impairment in verbal encoding efficiency, not retrieval difficulties. Assessment of false positive recognition errors indicated that resection of nonsclerotic left hippocampus selectively impaired the ability to encode stimulus uniqueness within correct semantic fields. The clinical and theoretical significance of these results are discussed.

Adult↗
PubMed1996

Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients.

Controversy exists as to whether hippocampal sclerosis (HS) is a preexisting cause or a consequence of seizures. We investigated 122 consecutive patients who underwent anterior temporal lobectomy for intractable epilepsy between 1989 and 1992. MRI scans were normal apart from evidence of HS in 5 cases. The degree of HS was graded from 0 to 4. There was a significant inverse correlation between age of seizure onset and grade of HS (P < 0.0001), and a positive correlation between duration of epilepsy and grade of HS (P < 0.001). Using a dichotomous grouping of HS (HPSC - for grades 0 and 1 [no/mild HS], and HPSC + for grades 3 and 4 [moderate/marked HS]), there was a positive correlation between HPSC + and a history of childhood febrile seizures (CFS) (P = 0.003), earlier age of onset of epilepsy (P < 0.001) and longer duration of epilepsy (P < 0.001). There was no correlation with history of particularly prolonged individual seizures. Partial correlations after controlling for age at onset of epilepsy showed that there was no longer a significant relationship between HPSC + and duration of epilepsy. After controlling for duration of epilepsy, the relationship between HPSC + and age of onset remained significant (P < 0.001). The correlation between HPSC + and CFS, controlling for age at onset, was not significant. A series of logistic regression analyses showed age at onset to be the only predictor of HPSC +. It is concluded that this is supportive evidence for preexisting HS being a cause of temporal lobe epilepsy and not a consequence of seizures.

Adult↗
PubMed1996

Intractable epilepsy due to meningitis: results of surgery and pathological findings.

Between 1986 and 1992, among a total of 668 craniotomies performed for intractable epilepsy, 13 (1.9%) patients had a presumed aetiology of a previous episode of meningitis. Twelve were investigated with chronic electrocorticography with subdural electrodes which showed mesial temporal onset in eight, regional temporal onset in three and bilateral diffuse onset in one. One patient underwent corpus callosotomy and 12 anterior temporal lobectomy (ATL) (6L, 6R). The pathology in the resection cases was hippocampal sclerosis in six and gliosis in six. Mean length of follow up was 3 years (range 1-6 years). Ten of the 12 (83%) ATL patients were seizure free (six off medications). Two ATL patients and the callosotomy patient were significantly improved. It is concluded that in patients where the presumed aetiology of intractable epilepsy is meningitis and widespread damage may therefore be expected, this does not necessarily indicate multifocality, and the prognosis following resective surgery appears to be good.

Adolescent↗
PubMed1996

Choroid plexus histoplasmoma: clinical, pathologic, and imaging findings.

Histoplasmosis of the choroid plexus has not previously been described. We report its occurrence, as well as its clinical, pathologic, and imaging characteristics in one case. Clinically, our patient's choroid plexus lesion produced encephalopathy and third nerve palsy. On imaging it appeared as a hemorrhage or calcification. Cerebrospinal fluid studies were consistent with a chronic meningeal process uncomplicated by hemorrhage. Stereotactic biopsy of the choroid plexus was required to establish the diagnosis of cerebral histoplasmosis. Pathologic examination also revealed prominent abnormal calcification, which permitted the lesion of masquerade as a hemorrhage on computed tomographic and magnetic resonance images.

Biopsy↗
PubMed1995

Opioid and tachykinin neuropeptides in prolactin-secreting human pituitary adenomas.

Two opioid neuropeptides, methionine enkephalin (ME) and beta-endorphin (BE), and one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries. Immunohistochemical techniques provided appropriate staining for PRL. Reversed-phase high performance liquid chromatography (RP-HPLC) was used to purify these three neuropeptides before their analysis, radioimmunoassay (RIA) was used for the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide SP-LI level is decreased, the POMC peptide BE level is not altered, and the proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.

Adenoma↗
PubMed1995

Reports by patients and their families of memory change after left anterior temporal lobectomy: relationship to degree of hippocampal sclerosis.

Memory decline represents the primary neuropsychological morbidity of anterior temporal lobectomy. Recent investigations using laboratory tests of memory have reported an association between the neuropathological status of the resected left mesial temporal region and memory outcome, with adverse memory outcome associated with a lack of significant left hippocampal pathology. The purpose of this investigation was to examine the relationship between the reports by the patients and their families of observed postoperative changes in day-to-day memory function and the degree of hippocampal sclerosis in resected left mesial temporal lobes. Twenty patients and a close family member (parent or spouse) of each of the patients completed standardized questionnaires assessing pre- to postoperative changes in verbal and spatial memory; these were related to the neuropathological findings. The results indicated that patients without left hippocampal sclerosis reported significantly worse memory outcome than those with hippocampal sclerosis. The ratings provided by the relatives of the patients yielded a comparable effect, and objective memory tests supported the reports by the patients and their families. The neuropsychological findings associated with left hippocampal pathology are of clinical significance and should be considered in surgical evaluation and in the counseling process.

Adult↗