Medial Temporal Lesions Research Articles

Neuropathological hallmarks in autopsied cases with mitochondrial diseases caused by the mitochondrial 3243A>G mutation.

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.

Like a rolling stone: Psychotherapy without (episodic) memory.

People with profound amnesia still retain the capacity to learn about the emotional value of experiences, which is crucial in developing and sustaining interpersonal relationships. In a 2017 paper, we demonstrated for the first time (with patient JL) that transferential feelings develop across the therapeutic process, despite profound episodic memory impairment after medial temporal lesions. This paper reports a second case (GA) of a profoundly amnesic patient in psychotherapy, this time after lesions to the anterior fornix. The work with GA opens issues such as the differences and similarities to the previous case, counter-transference phenomena, and the effects of hyperphagia. The findings make it clear that many phenomena are common to both GA and JL, such as forgetfulness, various types of repetition, the importance of the therapeutic alliance, and the ability to make therapeutic gain. However, there were differences between the cases, for example as regards confabulation, which may relate to either pre-morbid personality or lesion site. The paper also discusses the way in which patients of this type bear the very status of psychotherapeutic work with profoundly amnesic patients. Where others have seen barriers and in principle problems in working with such patients, we see many opportunities.

Dolichoectatic middle cerebral artery masquerading as cerebral cavernous malformation

Background: Intracranial dolichoectasia (IADE) is a rare vascular disease characterized by distension, elongation and tortuosity of an artery. IADE rarely involves pediatric aged groups. It is either asymptomatic or manifests as ischemic or hemorrhagic attacks.
 
 Case description: A healthy, 30-year-old, female teacher presented with recurrent attacks of bi-frontal headaches associated with dizziness and dropping attacks of two-week duration. She was referred by her general physician to our institution of Neurosurgery Teaching Hospital in Baghdad, Iraq with a suspicion of medial temporal lesion on a cranial computed tomography (CT) scan. Magnetic resonance imaging study excluded the diagnosis suggesting a dolichoectatic middle cerebral artery that was confirmed by CT-angiography. 
 
 Conclusion: Dolichoectasia of the middle cerebral artery is a rare and benign lesion. However, it can masquerade as cerebral cavernous malformation or intracranial arterial aneurysm. Thus, careful radiological evaluation with the suggested diagnostic criteria are of paramount importance to prevent its misdiagnosis.

MRI-Guided Stereotactic Laser Ablation of Deep-Seated Cerebral Cavernous Malformations

Abstract INTRODUCTION Magnetic resonance imaging (MRI)-guided stereotactic laser ablation (SLA) is a minimally invasive alternative to open surgery for symptomatic cerebral cavernous malformations (CCMs). While SLA of neocortical and medial temporal lesions is described, we examined the safety and effectiveness of SLA of deep-seated symptomatic CCMs in patients considered to be poor candidates for open resection. METHODS We analyzed 4 patients who presented with neurological symptoms associated with a CCM in deep brain structures. Each patient underwent CCM SLA with an effort to exclude adjacent brain parenchyma followed by standard clinical and imaging follow-up. RESULTS Three patients presented with chronic medically refractory headache and small lesions (0.1-2.6 cm3) consistent with CCM in thalamus (2) or putamen (1). A fourth patient presented with recurrent bleeding and hemiparesis associated with a large CCM (4.3 cm3) of the subthalamus/midbrain. Symptoms durations were 0.5 to 7 yr. SLA was performed using Visualase (Medtronic, Inc.); perilesional brain was monitored to avoid thermal injury. Out of 4 patients, all demonstrated a decrease in CCM volume and improvement of neurological symptoms at 5 to 23 mo follow-up. Two patients (one thalamus, one putamen), experienced evidence of hemorrhage during ablation (apparent with intraoperative MRI), limiting the extent of ablation in one case. Both patients were stabilized and made full recoveries. The ablation in subthalamus/midbrain was not associated with bleeding but did exacerbate hemiparesis, requiring rehabilitation. Hospital stays ranged from 2 to 5 d. CONCLUSION In a retrospective series, MR thermography guided SLA of symptomatic deep brain CCM was technically feasible. Unlike a prior series of more superficial epileptogenic CCM in which no hemorrhages were observed, SLA of deep CCM may carry higher risk of bleeding and neurological deficits. Larger, longer-term studies are required.

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect.

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200-300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)-the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL-mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200-300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.

Retrospective and prospective memory, short-term binding and executive functions’ abilities in two adolescents with medial temporal and frontal brain lesions: A virtual reality study

Retrospective and prospective memory, short-term binding and executive functions’ abilities in two adolescents with medial temporal and frontal brain lesions: A virtual reality study

Impact of combined medial temporal atrophy and white matter lesions on the cognitive and emotional functions in Alzheimer's disease patients

The purpose of this study was to determine the relationship between the combined presence of medial temporal atrophy (MTA) and white matter lesions (WMLs: periventricular hyperintensity (PVH) and deep white matter hyperintensity) and the cognitive/emotional function in Alzheimer's disease (AD) patients. The subjects included 193 patients with AD and 30 normal elderly controls. On MRI, MTA was rated using the Voxel-based specific regional analysis system for AD (VSRAD). WMLs was also estimated using the Fazekas scale. The MRI measurements were classified as follows: MTA=VSRAD<2 or ≥2; WML absent (-) 0/1 or present (+) 2/3. A total of five groups were assessed, including four groups with AD and a control group. The cognitive and emotional functions were evaluated with neuropsychological tests (Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS) and Apathy scale). Four AD groups showed significant declines in the both the MMSE and FAB scores compared to that observed in the control group ((***)p<0.001, (**)p<0.01, (*)p<0.05). Among these four AD groups, the MMSE and FAB scores of in the VSRAD<2 and WML (-) groups significantly declined to VSRAD≥2 and WML (+), respectively group ((*)p<0.05). VSRAD≥2 and WML (+) groups showed demonstrated significantly higher scores than the control group on the GDS ((*)p<0.05), and the PVH (+) group exhibited significantly higher scores than the control group on the apathy scale ((*)p<0.05). Multiple regression analysis identified a VSRAD score of ≥2 and the presence of WMLs to be most significantly associated with the cognitive and emotional functions. Combined presence of MTA and WML is associated with lower MMSE and FAB scores. Furthermore, depression is also associated with MTA and WML, while PVH independently affects the degree of apathy.

Dysglycemia, brain volume and vascular lesions on MRI in a memory clinic population

ObjectiveIt is unclear, if the association between abnormalities in glucose metabolism (dysglycemia) and impaired cognitive functioning is primarily driven by degenerative or vascular brain damage. We therefore examined the relation between dysglycemia and brain volume and vascular lesions on MRI in a memory clinic population. MethodsThe relations between markers of glycemia (HbA1c and fasting glucose levels) and normalized brain volume, medial temporal lobe atrophy and vascular lesions (white matter hyperintensities, lacunes) were assessed in 274 consecutive patients attending a memory clinic, using linear regression analyses. ResultsClinical diagnoses were subjective complaints (n=117), mild cognitive impairment (n=62), Alzheimer's disease (n=61) and other type of dementia (n=34). Twenty patients had a history of diabetes. Across the whole study population there was no relation between HbA1c or fasting glucose and the brain MRI measurements, after adjustments for age, sex and diagnostic group. Secondary analyses after stratification by diabetes status, diagnosis and median age (67years) did not change the results. ConclusionIn this memory clinic population, dysglycemia was not associated with either brain volume or vascular lesions. Apparently, dysglycemia is not associated with a specific class of brain pathology in patients with cognitive complaints.

A neuropsychological approach to time estimation

Time estimation, within a range of seconds, involves cognitive functions which depend on multiple brain regions. Here we report on studies investigating the reproduction and production of three durations (5, 14, and 38 seconds) in four groups of patients. The amnesic patient underproduced the length of the long durations because of episodic memory deficit following bilateral medial temporal lesions. Epileptic patients (n = 9) with right medial temporal lobe resections underproduced the three durations because of a distorted representation of time in long-term memory. Traumatic brain injury patients (n = 15) made more variable duration productions and reproductions because of working memory deficits following frontal-lobe dysfunction. Patients with Parkinson's disease (n = 18) overproduced the short duration and underproduced the long duration because of a possible increase in internal clock speed following levodopa treatment, as well as working memory deficits associated with frontal-lobe damage. Further research, in neurological and psychiatric patients, is required to better understand the underlying mechanisms of time estimation.

Surgical outcome in neocortical resections of type IIId focal cortical dysplasia with accompanying medial temporal pathology.

Focal cortical dysplasia (FCD) type IIId is a newly proposed type associated with early-life brain insults. Such patients are often considered unsuitable for resective epilepsy surgery, given the usually wide extent of the lesion and the poor correlation of MRI to the epileptogenic pathology. Two patients with intractable epilepsy, early-life ischemic/traumatic injury and MRI findings of extensive unilateral cystic-gliotic and ipsilateral medial temporal sclerotic-malformative lesions were subjected to presurgical evaluation revealing well-localized neocortical ictal onsets. They underwent tailored neocortical resections sparing medial temporal areas and achieved Engel class I postsurgical outcomes. Histopathology was consistent with type IIId focal cortical dysplasia. Successful outcomes with tailored resections may be achieved in cases with this subtype of focal cortical dysplasia, in the presence of converging and well-localized semiological, EEG and functional imaging data, even on a background of complex and extensive MRI abnormalities. Medial temporal pathology, although often present in this setting, is not necessarily the site of ictal onsets, and its resection may not be always mandatory for a favorable outcome.

The Middle Fossa Approach and Extended Middle Fossa Approach

The middle fossa approach and extended middle fossa approach, also known as the anterior transpetrosal approach, are cranial base techniques for addressing small vestibular schwannomas, medial temporal bone lesions, midbasilar trunk aneurysms, and selected petroclival lesions. To provide an outline of a number of technical nuances that are important to correct application of these approaches, maximizing exposure, and limiting potential morbidity. Via a temporal craniotomy, the petrous apex is removed in variable degrees, depending on the exposure requirements of the lesion. The technique is described in detail with appropriate nuances of the technique provided. The described nuances of technique in the performance of the approaches have resulted in successful application of these techniques in a significant number of cases. Significant familiarity and practice with these surgical approach techniques are critical to applying them safely to clinical problems. A number of technical details can assist the surgeon in achieving optimal exposure and limited morbidity.

One‐year cholesterol lowering treatment reduces medial temporal lobe atrophy and memory decline in stroke‐free elderly with atrial fibrillation: evidence from a parallel group randomized trial

In elderly patients with atrial fibrillation (AF), medial temporal lobe (MTL) atrophy and white matter lesions (WML) may account for the cognitive decline. Though a combination therapy of statins with cholesterol lowering agents like ezetimibe may be beneficial in patients with AF, its effects on MTL structure and WML remains unknown. A parallel group double-blinded randomized trial was performed during 1 year whereby elderly stroke-free AF patients either received placebo or atorvastatin and ezetimibe on top oral anticoagulation therapy. Neuropsychological performance and inflammatory markers in the blood were assessed at baseline and 1 year later together with amygdala and hippocampal volume as well as WML. Sixty-three patients were assessed for eligibility, but 29 patients had to be excluded so that 34 patients were randomized to both groups. In the treatment group, the systemic level of inflammation was significantly decreased after 1 year and an improvement in cognitive speed as well as short- and long-term memory was observed. While there was no significant difference in MTL volume at baseline, the placebo group exhibited more atrophy for right amygdala and left hippocampus at follow-up. Finally, descriptive data showed a slight decline of WML volume in the treatment group. In spite of limitations due to small sample size, our data suggest that intensive cholesterol lowering therapy in AF patients may slow cognitive decline and atrophy of the MTL. Though these results have to be replicated in a larger sample, they offer potential for future interventions.

Acute disseminated encephalomyelitis with medial temporal lesions mimicking acute limbic encephalitis

We describe a 59-year-old Japanese man with acute disseminated encephalomyelitis (ADEM) demonstrating medial temporal lesions on magnetic resonance images (MRI) mimicking acute limbic encephalitis. This patient had antecedent infection and developed urinary retention. Subsequently he showed various neurological manifestations including truncal ataxia, nystagmus and generalized convulsions, suggesting multifocal brain and spinal cord lesions. Brain MRI demonstrated hyperintensity areas restricted to the left hippocampus, amygdala, and inferior temporal gyrus. The cerebrospinal fluid did not show any pleocytosis or elevated protein levels, and had no evidence of herpes virus infection. Serum antineuronal antibodies were not identified. Corticosteroid therapy markedly improved the symptoms. Although these clinical features indicating multifocal central nervous system lesions were compatible with those of ADEM, none of the previously reported patients with ADEM showed lesions confined to the medial temporal lobes mimicking acute limbic encephalitis. Medial temporal lesions are characteristic features of herpetic or non-herpetic acute limbic encephalitis. Findings in our patient suggest that non-herpetic limbic encephalitis patients showing marked response to

Cognitive mapping through electrophysiology

Cognitive mapping through electrophysiology

Psychomotor seizures, Penfield, Gibbs, Bailey and the development of anterior temporal lobectomy: a historical vignette.

Psychomotor seizures, referred to as limbic or partial complex seizures, have had an interesting evolution in diagnosis and treatment. Hughlings Jackson was the first to clearly relate the clinical syndrome and likely etiology to lesions in the uncinate region of the medial temporal lobe. With the application of electroencephalography (EEG) to the study of human epilepsy as early as 1934 by Gibbs, Lennox, and Davis in Boston, electrical recordings have significantly advanced the study of epilepsy. In 1937, Gibbs and Lennox proposed the term "psychomotor epilepsy" to describe a characteristic EEG pattern of seizures accompanied by mental, emotional, motor, and autonomic phenomena. Concurrently, typical psychomotor auras and dreamy states were produced by electrical stimulation of medial temporal structures during epilepsy surgery by Penfield in Montreal. In 1937, Jasper joined Penfield, EEG was introduced and negative surgical explorations became less frequent. Nevertheless, Penfield preferred to operate only on space occupying lesions. A milestone in psychomotor seizure diagnosis was in the year 1946 when Gibbs, at the Illinois Neuropsychiatric Institute, Chicago, reported that the patient falling asleep during EEG was a major activator of the psychomotor discharges and electrographic ictal episodes becoming more prominently recorded. Working with Percival Bailey, Gibbs was proactive in applying EEG to define surgical excision of the focus in patients with intractable psychomotor seizures. By early 1950s, the Montreal group began to clearly delineate causative medial temporal lesions such as hippocampal sclerosis and tumors in the production of psychomotor seizures.

Effects of neonatal medial versus lateral temporal cortex injury: Theoretical comment on Malkova et al. (2010).

The article by Malkova, Mishkin, Suomo, and Bachevalier (2010, this issue) adds an important piece to our understanding of the role of the medial versus lateral temporal regions in socioemotional behavior. In their paper, they evaluate the effect of infant and adult amygdala lesions and infant inferotemporal cortex lesions on the social interactions of monkeys in infancy and adulthood. The results show that medial temporal lesions performed in infants produce greater effects on socioaffective behavior than similar lesions in adulthood and that infant monkeys with inferotemporal lesions exhibit social deficits that are resolved by adulthood. These results are relevant to three significant issues: (1) the role of the medial temporal and lateral temporal cortex in the symptoms of the Kluver-Bucy syndrome; (2) the role of age at injury in behavioral change after cerebral injuries; and (3) the importance of lesion locus and behavioral measure for recovery from infant and adult cerebral injury.

Recollection and familiarity for public events in neurologically intact older adults and two brain-damaged patients

Despite extensive investigations of the role of recollection and familiarity on laboratory-acquired memories, there is a dearth of such research on memories formed in real life settings. We used the Remember/Know paradigm to investigate the relative contribution of recollection and familiarity processes to memory of public historical events reported in the media across the life span of two groups of neurologically intact older adults (old-old: 74–85, young-old: 58–69) and on two patients with brain damage. First, in neurologically intact participants, recollection rates decreased as a function of time elapsed since the event occurred, at a significantly higher rate than the corresponding decrease in familiarity or global memory. Second, consistent with the hypothesis that memories become increasingly semantic as they age, and that recollection is selectively impaired in older adults, across decades, old-old participants exhibited lower recollection, but not familiarity, relative to young-old participants. Finally, as a demonstration of how this procedure may be applied to studies of clinical populations, we tested two patients, one with medial temporal lesions and another with relative sparing of the medial temporal lobes, but with anterior temporal damage. We found that recollection was disproportionately impaired relative to familiarity across most of the life span in the patient with medial temporal lesions severely while recollection was relatively intact in the patient with anterior lateral temporal damage. We discuss the present results in the context of neuroanatomical and process-oriented theories of how memories age.

The Italian Brain Normative Archive of structural MR scans: norms for medial temporal atrophy and white matter lesions

To describe the clinical and neuropsychological features of a large group of cognitively intact persons subjected to brain high-resolution magnetic resonance (MR), to compare them with the general population, and to set norms for medial temporal atrophy and white matter lesions. Participants in the Italian Brain Normative Archive (IBNA) study were 483 consecutive volunteers undergoing MR for reasons unrelated to cognition (migraine or headache, visual and balance or auditory disturbances, paresthesias, and others) and showing no brain damage. Manual tracing of hippocampal and amygdalar volumes and visual rating of white matter lesions were made. The whole study group was stratified by age (</=60 and 60+ yrs) and by the reason for MR prescription. In the whole group, mean age and education were 52.4+/-13.7 and 9.8+/-4.2 years, respectively, and the prevalence of women was 63%. Clinical, neuropsychological and morphometric features were similar in the stratified subgroups. Neuropsychological features were those expected for age and education based on Italian normative values. Hippocampal and amygdalar volumes were not associated with age, except for the right amygdala (B -0.159, 95% CI -0.28 to -0.03, p=0.016). Persons in the IBNA study had clinical and neuropsychological features consistent with that of the general population. Their brain morphometric features may be used as normative references for patients with suspected neurodegenerative disorders.

Large Congenital Melanotic Nevi in an Extremity with Neurocutaneous Melanocytosis

A 14-day-old boy presented with a large congenital melanocytic nevus over his left thigh with approximately 17 satellite nevi distributed over the rest of his skin surface. Six weeks later, he developed generalized tonic-clonic seizures and additional satellite nevi became apparent (n > 20). A subsequent brain magnetic resonance imaging demonstrated right temporal T1 hyperintense signal abnormality. At 4 months of age the patient underwent a lumbar puncture that was normal without evidence of melanocytes or tumor. Nevertheless, a few days later he underwent resection of his right medial temporal lesion which demonstrated melanocytosis in the temporal lobe as well as melanocytosis in subependymal areas in other parts of the brain and ventricles, confirming the suspected diagnosis of neurocutaneous melanocytosis. Our case supports previous studies that conclude that the number of satellite nevi is a greater predictor of neurocutaneous melanocytosis than is the location of large congenital melanocytic nevus. In our case, cerebrospinal fluid studies were not reliable even in the face of florid neurocutaneous melanocytosis involving the leptomeninges and ventricles.

Bilateral medial temporal lesions in Japanese encephalitis

A 62-year-old woman presented with headache, fever, and deteriorating consciousness. Brain MRI showed bilateral lesions of the thalamus and substantia nigra. The medial temporal region was also involved bilaterally (figure). The serum hemagglutination inhibition test for Japanese encephalitis …