Mammillary Bodies Research Articles

Young pregnant woman with hyperemesis gravidarum and cognitive alterations

A 26-year-old woman, 21.6 weeks gestation, was diagnosed with hyperemesis gravidarum a month earlier. She continued with vomiting and started with weakness in extremities, unsteadiness and slurred speech. She was hospitalized, had hypokalemia (2 mEq/L), received intravenous potassium phosphate replacement, and was discharged. One week later, she started with dizziness and confusion. In the disease course, she received medical attention focused on the apparent weakness and gastrointestinal alterations. Three weeks later, the patient started with inattention, and she came to our institution. For this time, she had developed nystagmus, inability to complete eye movements, confabulation and confusion. The diagnosis then was Wernicke-Korsakoff encephalopathy, a neurological complication of thiamine deficiency. MRI was the primary tool to confirm the diagnosis showing hyperintensity in the paramedian thalamic region, periaqueductal grey matter and mammillary bodies. She was discharged after treatment in better condition but still with cognitive and coordination problems. Management should begin as soon as possible with thiamine substitution; the delay will cause more important neurological sequelae and increase mortality up to 10 to 20%.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

Wernicke's encephalopathy: rare complication of hyperemesis gravidarum

Wernicke’s encephalopathy is a rare disease, resulting from severe thiamine deficiency (vitamin B1). Alcoholic subjects are most often affected, but it may occur outside of this addiction. Magnetic resonance imaging is the gold standard imaging modality to confirm the diagnosis. This pathology manifests itself in T2-weighted hyperintensity in the periaqueducal, thalami and mammillary bodies. A suitable treatment makes it possible to avoid heavy sequelae. We report the case of a 23-year-old woman, pregnant with 12 weeks of amenorrhea, with diplopia, headache and abundant vomiting, reffering to Wernicke’s encephalopathy. Key words: Wernicke’s encephalopathy, vitamin B1, Magnetic resonance imaging, hyperemesis gravidarum.

Abstract- Poster

INTRODUCTION:Wernicke’s encephalopathy presents as a triad of ataxia, global confusion and ophthalmoplegia. It can have multiple causes; Hyperemesis gravidarum is one of the causative factors. It results in severe vomiting in pregnancy resulting in dehydration. This can lead to acute deficiency of thiamine, which can manifest as Wernicke’s encephalopathy. Poor nutritional intake, depletion of stores and and increased demands of pregnancy can also result in Wernicke’s.MRI Brain is both specific and sensitive for diagnosis.Case summary –A 25 year old married, primi-gravida hailing from urban background belonging to middle socio-economic status, presented at 16 weeks of gestation with complaints of 6 weeks history of severe vomiting, talking irrelevantly, disturbed sleep and weakness of all four limbs. Symptoms progressed over a week with total inability to ambulate and confusion. Clinically she had signs of minimal power and loss of tone, ataxic gait and disorientation. However no ophthalmoplegia was noted. Routine blood investigations were within normal limits. MRI Brain revealed hyperintensities in thalamus and mammillary bodies. A diagnosis of Wernicke’s encephalopathy was made and treatment was instituted with high dose parental thiamine. She reported significant improvement in symptoms over the next 2 weeks.DISCUSSION AND CONCLUSION-Hyperemesis gravidarum is one of the treatable causes of Wernicke’s encephalopathy. It requires a high degree of clinical suspicion. Neurologic outcomes are usually good, however pregnancy outcomes vary.

Evaluation of the Usefulness of an Expandable Stent for Establishing Patency in Endoscopic Third Ventriculostomy: A Fresh Cadaveric Study.

To demonstrate the feasibility of stent application to the third ventricular floor during endoscopic third ventriculostomy (ETV). We performed the ETV procedure on four fresh cadavers not exposed to head trauma. The neuroendoscope was introduced into the third ventricle under ultrasonography guidance. The stoma was opened with a neuroballoon in the third ventricular floor in three cases and with the catheter carrying the stent in the remaining case. The balloon-expandable stent was 8 mm in length and 4 and 4.5 mm in diameter. The distal end of the stent was placed in the prepontine cistern, without contact with the vascular structures in the cistern, and the proximal end was placed in the stoma, with its proximal end in the third ventricle. In all the cases, the stent was fixed in the targeted position. Then, the head cavity was opened. The brain was extracted from the skull for pathological analysis. The stents were placed in front of the mamillary bodies in all four cases, fixed around the stoma, which was opened previously. No significant compression on the structures around the prepontine cisterna and on the basilar artery was observed. Expandable stents may be useful and technically safe in creating and maintaining the stomal opening in ETV.

Exploring immunoreactivity of TTF-1 and AVP in hypothalamic hamartoma.

Hypothalamic hamartoma (HH) is a rare developmental disorder presenting with gelastic seizures or precocious puberty attributed to gonadotrophin-releasing hormone expression by the hamartoma. The histogenesis of HH is uncertain, and diagnosis of HH is difficult in small biopsies due to its close resemblance to normal hypothalamic nuclei. TTF-1 and arginine vasopressin (AVP) are associated with gonadotropin-releasing hormone release. In this study, we explored the expression pattern of TTF-1 and AVP in HH and its utility, if any, in diagnosis. We reviewed the clinical, radiologic, and histopathological features of 23 HH diagnosed over the past decade at our Institute. The age at presentation ranged from 11 months to 34 years with gelastic seizures (82.6%), precocious puberty (17.4%), and developmental delay (8.7%) as presenting symptoms. On imaging, all the lesions (n = 9) involved the posterior and tuberal group of hypothalamic nuclei, while 5 cases involved the anterior hypothalamus. Anatomically, the lesions involved mammillary body, arcuate and periventricular nuclei. On histopathology, 52% cases revealed nodular arrangement of small neurocytic cells separated by glial stroma. TTF-1 and AVP immunoreactivity was absent in all the cases, whereas in normal hypothalamus, AVP was expressed in periventricular nuclei. Our results suggest that immunoexpression of TTF-1 is absent in HH, particularly in those arising from the posterior hypothalamus, and this can be used in small biopsies to distinguish from a normal hypothalamus as well as from posterior pituitary tumors.

Atrophy of mammillary bodies in early stages of Alzheimer’s disease

AbstractBackgroundThe mammillary bodies (MB) share direct connections with key components of memory circuitry including the hippocampus. Additionally, MB atrophy is present in a number of clinical conditions including late stages of Alzheimer’s disease (AD); however, whether MB atrophy occurs in early stages of AD remains unclear. Voxel‐Based Morphometry (VBM) was conducted to determine whether structural changes to MB are an early feature of AD and to quantify the association between MB atrophy and performance on neurocognitive assessments.MethodThis cross‐sectional study included subjects (n=470) from the Alzheimer’s Disease Neuroimaging Initiative aged ≥ 50 years with volumetric T1‐weighted MR scans at 3 Tesla and cerebrospinal fluid (CSF) AD biomarkers. Normal cognition (cognitively normal, CN, and preclinical AD) was defined as Clinical Dementia Rating (CDR) of 0. Based on previously established criteria, CN subjects (n=112) were negative for CSF AD pathology, while preclinical AD (n=39), early mild cognitive impairment (EMCI, n=108), late mild cognitive impairment (LMCI, n=100), and AD (n=111) subjects were positive for CSF AD pathology. Average grey matter (GM) densities in the MB, hippocampus, and cerebellar vermis were assessed by VBM (SPM12 with MarsBaR toolbox).ResultGM densities in MB and hippocampi decreased with worsening clinical severity with significant differences beginning in the EMCI stage for both regions. Compared to CN subjects, the relative decrease in GM densities was greater in MB than in the hippocampi in EMCI, LMCI, and AD subjects. Cerebellar vermian GM densities were similar across all groups. Adjusting for age and sex, MB GM densities were associated with CSF levels of amyloid‐β42 (β=0.189, p<0.001) but not with tau or phosphorylated‐tau181 (p>0.05). Hippocampal GM densities were associated with all CSF AD biomarkers (p<0.05). Adjusting for age, sex, and education, MB and hippocampal GM densities were associated with Mini‐Mental State Examination (MB: β=0.270, p<0.001, hippocampi β=0.512, p<0.001) and CDR Sum of Boxes (MB: β=‐0.337, p<0.001, hippocampi: β=‐0.561, p<0.001).ConclusionEvidence for MB atrophy was found in early stages of AD and increased with clinical severity, correlating with CSF amyloid‐β42 and neurocognitive measures. These findings support MB atrophy as an early manifestation of AD.

Hippocampal neuropeptide Y2 receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

IntroductionThe neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2 receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear. MethodsHere, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions. ResultsThe acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies. ConclusionsThese findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.

Two Cases of Wernicke’s Encephalopathy: A Rare Complication of Hyperemesis Gravidarum

Wernicke's encephalopathy (WE) is a serious neurologic condition resulting from thiamine deficiency (vitamin B1). The majority of cases involve alcoholism; however, nonalcohol-associated WE do occur and is under-recognized. Magnetic resonance imaging is the gold standard imaging modality to confirm the diagnosis. We report two cases of young women with abundant vomiting during the first trimester of pregnancy (hyperemesis gravidarum), causing symptomatic Wernicke’s encephalopathy. The diagnostic was made by MRI showing a T2-weighted hyperintensity in the periaqueducal, thalami and mammillary bodies. However, it is imperative that WE is diagnosed and treatment is started as quickly as possible.

An extended Human Connectome Project multimodal parcellation atlas of the human cortex and subcortical areas.

A modified and extended version, HCPex, is provided of the surface-based Human Connectome Project-MultiModal Parcellation atlas of human cortical areas (HCP-MMP v1.0, Glasser et al. 2016). The original atlas with 360 cortical areas has been modified in HCPex for ease of use with volumetric neuroimaging software, such as SPM, FSL, and MRIcroGL. HCPex is also an extended version of the original atlas in which 66 subcortical areas (33 in each hemisphere) have been added, including the amygdala, thalamus, putamen, caudate nucleus, nucleus accumbens, globus pallidus, mammillary bodies, septal nuclei and nucleus basalis. HCPex makes available the excellent parcellation of cortical areas in HCP-MMP v1.0 to users of volumetric software, such as SPM and FSL, as well as adding some subcortical regions, and providing labelled coronal views of the human brain.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus

Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Anterior thalamic NMDA-induced damage impairs extrapolation relying on serial stimulus patterns, in rats

Extrapolation of serial stimulus patterns seems to depend upon identification and application of patterns relating sequences of stimuli stored in memory, thus allowing prediction of pending events never experienced before. There have been proposals that such a “generator of predictions system” would include the subiculum, mammillary bodies, anteroventral thalamus and cingulate cortex (e.g., Gray, 1982). The anteroventral thalamus (AVT) seems to be in a strategic position, both hodologically and experimentally, to allow testing of this hypothesis. This study investigated the effect of NMDA-induced damage to the anteroventral thalamus [part of the anterodorsal (AD) thalamus was also damaged in some animals], following stereotaxic minute topic microinjections, on the ability of male Wistar rats to extrapolate relying on serial stimulus patterns. Corresponding sham-operated controls received phosphate-saline buffer microinjections at the same stereotaxic coordinates. The subjects were trained to run through a straight alleyway along 31 sessions, one session per day, to get rewarded. Each session included four successive trials. Subjects exposed to the monotonic serial pattern received 14, 7, 3, 1 sunflower seeds along trials. Subjects exposed to the non-monotonic serial pattern received 14, 3, 7, 1 sunflower seeds. On the 32nd testing session, a fifth trial, never experienced before, was included immediately after the fourth trial. Sham-operated control subjects exposed to the monotonic serial pattern were expected to exhibit longer running times, since the content of their prediction in the fifth trial should be “less than 1 sunflower seeds”. In contrast, control subjects exposed to the non-monotonic serial pattern were expected to exhibit shorter running times, since the content of their prediction would be “more than 1 sunflower seeds”. Confirming these predictions, control subjects exposed to the monotonic serial pattern exhibited longer running times as compared to both, their own running times in previous trials within the same session and control subjects exposed to the non-monotonic schedule, thus indicating the occurrence of extrapolation. In contrast, AVT/AD lesioned subjects exposed to the monotonic schedule did not exhibit this increase in running times on the fifth trial, indicating lack of extrapolation. These results indicate that extrapolation relying on serial stimulus patterns is disrupted following extensive NMDA-induced damage to AVT and part of the AD. This represents the first consistent demonstration that the anterior thalamic nuclei are required for extrapolation of serial stimulus patterns and generation of predictions.

Non-alcoholic Wernicke's encephalopathy with atypical brain MRI in setting of severe subacute malnutrition

Wernicke encephalopathy (WE) classically presents as encephalopathy, oculomotor dysfunction, and gait ataxia. WE usually occurs in the setting of chronic alcohol use and thiamine insufficiency. MRI imaging generally demonstrates edema of the periaqueductal region of the midbrain, mammillary bodies, and thalamus. Basal ganglia (BG) involvement, more commonly seen in pediatric WE, is classically thought to differentiate pediatric versus adult WE. However, we report a case of adult non-alcoholic WE with both thalamic and BG involvement.

F-18 Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Showing Mammillary Body Involvement in a Case of Autoimmune Anti-N-Methyl D-Aspartate Antibody Encephalitis.

Autoimmune encephalitis with antibodies against neuronal cell surface antigens is a group of neuropsychiatric disorders, with anti-N-methyl D-aspartate (NMDAR) encephalitis being one of them. We report a case of a young male patient who presented with complaints of seizures associated with fever, rapidly progressing memory loss, and choreoathetoid movements for 1 month. His serum was strongly positive for anti-NMDAR receptor antibodies. F-18 fluorodeoxyglucose positron-emission tomography/computed tomography for the brain revealed hypermetabolism involving bilateral basal ganglia and bilateral mammillary bodies associated with hypometabolism in bilateral occipital lobes.

Difficult differential diagnosis between neuromyelitis optica spectrum disorder (NMOSD) and wernicke encephalopathy (WE). Case report

NMOSD and WE could share similar clinical and neuroradiological manifestations. Differential diagnosis is difficult when NMOSD occurs with area postrema syndrome or mental status changes and when T2 hyperintense lesions involve thalamus, hypothalamus, periventricular and periacqueductal regions [1,3]. The involvement of mammillary bodies in NMOSD is rare [2].

A deep learning toolbox for automatic segmentation of subcortical limbic structures from MRI images

A tool was developed to automatically segment several subcortical limbic structures (nucleus accumbens, basal forebrain, septal nuclei, hypothalamus without mammillary bodies, the mammillary bodies, and fornix) using only a T1-weighted MRI as input. This tool fills an unmet need as there are few, if any, publicly available tools to segment these clinically relevant structures. A U-Net with spatial, intensity, contrast, and noise augmentation was trained using 39 manually labeled MRI data sets. In general, the Dice scores, true positive rates, false discovery rates, and manual-automatic volume correlation were very good relative to comparable tools for other structures. A diverse data set of 698 subjects were segmented using the tool; evaluation of the resulting labelings showed that the tool failed in less than 1% of cases. Test-retest reliability of the tool was excellent. The automatically segmented volume of all structures except mammillary bodies showed effectiveness at detecting either clinical AD effects, age effects, or both. This tool will be publicly released with FreeSurfer (surfer.nmr.mgh.harvard.edu/fswiki/ScLimbic). Together with the other cortical and subcortical limbic segmentations, this tool will allow FreeSurfer to provide a comprehensive view of the limbic system in an automated way.

Distribution of brain oxytocin and vasopressin V1a receptors in chimpanzees (Pan troglodytes): comparison with humans and other primate species.

Despite our close genetic relationship with chimpanzees, there are notable differences between chimpanzee and human social behavior. Oxytocin and vasopressin are neuropeptides involved in regulating social behavior across vertebrate taxa, including pair bonding, social communication, and aggression, yet little is known about the neuroanatomy of these systems in primates, particularly in great apes. Here, we used receptor autoradiography to localize oxytocin and vasopressin V1a receptors, OXTR and AVPR1a respectively, in seven chimpanzee brains. OXTR binding was detected in the lateral septum, hypothalamus, medial amygdala, and substantia nigra. AVPR1a binding was observed in the cortex, lateral septum, hypothalamus, mammillary body, entire amygdala, hilus of the dentate gyrus, and substantia nigra. Chimpanzee OXTR/AVPR1a receptor distribution is compared to previous studies in several other primate species. One notable difference is the lack of OXTR in reward regions such as the ventral pallidum and nucleus accumbens in chimpanzees, whereas OXTR is found in these regions in humans. Our results suggest that in chimpanzees, like in most other anthropoid primates studied to date, OXTR has a more restricted distribution than AVPR1a, while in humans the reverse pattern has been reported. Altogether, our study provides a neuroanatomical basis for understanding the function of the oxytocin and vasopressin systems in chimpanzees.

Forniceal and hippocampal atrophy in temporal lobe epilepsy patients with a history of complex febrile convulsion

Objectives: Temporal lobe epilepsy (TLE) is the most common seizure type in adults. Recent studies showed that 28–58% of TLE patients had a previous history of complex febrile convulsions (CFC). We compared the hippocampal volumes and volumes of amygdaloid body and widths of fornix and mammillary bodies on magnetic resonance imaging (MRI) of TLE patients with and without history of CFC. Methods: MRI scans of 42 subjects retrospectively examined. The amount of atrophy in hippocampus, amygdaloid body, fornix and mammillary bodies were determined by two formulas depending on the mean values of the controls. Results: We found no difference between TLE patients with a history of CFC and TLE patients without such a history in terms of all the quantitative measurements results (p>0.05) except the absolute right-left hippocampus volume and fornix % difference rate (p<0.01, p<0.05 respectively). Conclusion: Forniceal atrophy was more prominent in the TLE group of patients with previous CFC history when compared to those patients without a CFC history. The CFCs should not be underestimated in the childhood, as they are associated with more atrophy in the particular brain structures in patients with TLE.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas.

Repetitive transcranial magnetic stimulation during a spatial memory task leads to a decrease in brain metabolic activity

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is able to generate causal-based interferences between brain networks and cognitive or behavioral responses. It has been used to improve cognition in several disease models. However, although its exploration in healthy animals is essential to attribute its pure effect in learning and memory processes, studies in this regard are scarce. We aimed to evaluate whether rTMS leads to memory facilitation in healthy rats, and to explore the brain-related oxidative metabolism. We stimulated healthy Wistar rats with a high-frequency (100 Hz) and low-intensity (0.33 T) protocol during three consecutive days and evaluated the effect on the performance of an allocentric spatial reference learning and memory task. Following the last day of learning, we assessed oxidative brain metabolism through quantitative cytochrome c oxidase (CCO) histochemistry. The results showed that rTMS did not improve spatial memory in healthy rats, but the behavioral outcome was accompanied by a CCO reduction in the prefrontal, retrosplenial, parietal, and rhinal cortices, as well as in the striatum, amygdala, septum, mammillary bodies, and the hippocampus, reflecting a lower metabolic activity. In conclusion, rTMS induces a highly efficient use of brain regions associated with spatial memory.