Hypergonadotrophic Hypogonadism with Cerebellar Ataxia in a Twenty-Six-Year-Old Female: A Case Report

Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Median Nerve Somatosensory Evoked Potentials in Patients with Chiari Malformation

Abnormal SEP reflects dysfunction of the medial lemniscus and posterior cervical cord. These structures are likely to be affected in Chiari malformation. Therefore, SEP abnormalities may provide valuable information in patients with CM. However, the consistency of SEP abnormality or normality with the damage is a matter of research. Knowing whether median nerve somatosensory evoked potential (SEP) is useful in revealing subclinical damage in patients with Chiari malformation is important in the treatment and follow-up plan of the disease. The aim of this study was to investigate the relationship between median nerve SEP values and the severity of cerebellar ectopia in patients with Chiari type 1 malformation. Median nerve SEP values were obtained from 30 healthy individuals and 146 individuals with Chiari malformation. The cerebellar ectopia degree and McRae line length were measured. SEP values were not significantly different between groups. The McRae line was found to be significantly shorter in the control group than in the Chiari malformation group (p = 0.031). There was no correlation between the degree of cerebellar ectopia and the length of the McRae line (r = 0.002, p = 0.979). Neither cerebellar ectopy degree nor McRae line length had a relationship with SEP values (r = -0.153, p = 0.066;r = -0.056, p = 0.500, respectively). There was no difference in cerebellar ectopy degree or SEP values between the groups with cerebellar ectopy with and without a syrinx (p = 0.899;p = 0.080, respectively). Likewise, McRae line length was not found to be related to the presence of a syrinx (p = 0.139). Median nerve SEP examination was not beneficial for diagnosing asymptomatic-oligosymptomatic Chiari malformation as a subclinical injury, whether accompanied by syringomyelia or not.

Electricity: Past and Future or Black Holes and Green Planet

“Something is rotten in the state of Denmark”. These words of Shakespeare remember us that any small case can be connected with wider situation in the Globe. We would like to understand how changes electrical systems in time and what we will get in future. But what we know today about our home? Prominent scientists - physicists connect the past and future of our world with the formation and changes of black holes. “A black hole is a region of space-time whose gravitational attraction is so strong that even objects moving at the speed of light cannot leave it.” “A super massive black hole is a black hole with a mass of 105 - 1011 solar masses. Super massive black holes have been found at the center of many galaxies, including the Milky Way. Our galaxy revolves around a super massive black hole. This position of stellar bodies should be preserved for hundreds of millions of years.”

Middle cerebellar peduncles:Magnetic resonance imaging and pathophysiologic correlate

We describe common and less common diseases that can cause magnetic resonance signal abnormalities of middle cerebellar peduncles(MCP), offering a systematicapproach correlating imaging findings with clinical clues and pathologic mechanisms. Myelin abnormalities, different types of edema or neurodegenerative processes, can cause areas of abnormal T2 signal, variable enhancement, and patterns of diffusivity of MCP. Pathologies such as demyelinating disorders or certain neurodegenerative entities(e.g., multiple system atrophy or fragile X-associated tremor-ataxia syndrome) appear to have predilection for MCP. Careful evaluation of concomitant imaging findings in the brain or brainstem; and focused correlation with key clinical findings such as immunosuppression for progressive multifocal leukoencephalopahty; hypertension, post-transplant status or high dose chemotherapy for posterior reversible encephalopathy; electrolyte disorders for myelinolysis or suspected toxic-drug related encephalopathy; would yield an appropriate and accurate differential diagnosis in the majority of cases.

Cerebellar artery infarction with sudden hearing loss and vertigo as initial symptoms: A case report

BACKGROUND Sudden hearing loss(SHL)is associated with serious systematic conditions such as neoplasms,vascular events,autoimmune diseases,infections,and iatrogenic injury.Some authors report that SHL can be an early warning sign of impending vertebrobasilar ischemic stroke.It is important to distinguish stroke from benign disease.CASE SUMMARY A 48-year-old male patient presented with SHL and vertigo as first symptoms.Diffusion-weighted imaging revealed high signal intensity in the left posterior inferior cerebellar artery territory of the cerebellar hemisphere and high signal intensity in the right pons and bridge cerebellar arm,confirming that the patient had cerebral infarction.Treatment with antiplatelet drugs,steroid antiinflammatory drugs,and neurotrophic nerve therapy promoted blood circulation and removed blood stasis,and the symptoms of the patient were significantly improved.CONCLUSION SHL and vertigo could be the initial symptoms of vertebrobasilar ischemic stroke.

Effect of extracranial electric stimulation at cerebellar fastigial nucleus on serum C-reactive protein of patients with acute cerebral infarction

BACKGROUND： Some reports indicate that electric and/or chemical stimulation at various brain sites of experimental animals can raise regional cerebral blood flow and improve cerebral circulation; however, its mechanism is still unclear.OBJECTIVE： To observe the effects of electric stimulation at cerebellar fastigial nucleus on serum C-reactive protein of patients with acute cerebral infarction.DESIGN： Non-randomized synchronized contrast study.SETTING： The Second People＇s Hospital of Xinxiang City.PARTICIPANTS： A total of 54 patients with acute cerebral infarction were selected from the Department of Neurology, the Second People＇s Hospital of Xinxiang from December 2005 to December 2006. There were 31 males and 23 females, and their ages ranged from 56 to 80 years. All patients met the diagnostic criteria of the Fourth National Cerebrovascular Academic Meeting, were finally diagnosed by using CT examination,and provided the confirmed consent. Based on therapeutic demands, patients were divided into electric stimulation group and routine treatment group with 27 cases in each group. In addition, 21 healthy subjects,including 11 males and 10 females and aging 53 - 78 years, were selected as the control group. All the subjects in the control group did not have any histories of cerebrovascular diseases and severe body diseases.METHODS： Based on routine drug therapy, patients in the electric stimulation group were also treated by using CVFT-010M cerebral circulation function therapeutic device （made in Shanghai）. Electrode was fixed at bilateral mastoid in the first group and at extensible sides of upper limbs in the second group. Electric stimulation was given twice a day and lasted for 30 minutes each time. Ten days were regarded as a course.Parameters of device： mode Ⅲ, frequency 198%, and intensity 90% - 110% （bionic current）. Patients in the routine treatment group received the routine drug treatment. Content of serum C-reactive protein was measured in both electric stimulation group and routine treatment group before treatment and at 20 days after treatment, while in the control group on the exact day of health examination by using immunization.MAIN OUTCOME MEASURES： Level of serum C-reactive protein in the three groups.RESULTS： All 54 patients with acute cerebral infarction and 21 healthy subjects were involved in the final analysis. Level of serum C-reactive protein was higher in both electric stimulation group and routine treatment group than that in the control group before treatment （P 〈 0.01）. While, level of serum C-reactive protein was lower in the electric stimulation group than that in the routine treatment group after electric stimulation at cerebellar fastigial nucleus （P 〈 0.01）.CONCLUSION： Electric stimulation at cerebellar fastigial nucleus can decrease level of serum C-reactive protein in patients with acute cerebral infarction, and this may be one of the therapeutic mechanisms for curing acute cerebral infarction.

Heat stroke induced cerebellar dysfunction:A “forgotten syndrome”

We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature.

Angioplasty and stenting for severe vertebral artery orifice stenosis: effects on cerebellar function remodeling verified by blood oxygen level-dependent functional magnetic resonance imaging

Vertebral artery orifice stenting may improve blood supply of the posterior circulation of the brain to regions such as the cerebellum and brainstem. However, previous studies have mainly focused on recovery of cerebral blood flow and perfusion in the posterior circulation after interventional therapy. This study examined the effects of functional recovery of local brain tissue on cerebellar function remodeling using blood oxygen level-dependent functional magnetic reso- nance imaging before and after interventional therapy. A total of 40 Chinese patients with severe unilateral vertebral artery orifice stenosis were enrolled in this study. Patients were equally and randomly assigned to intervention and control groups. The control group received drug treat- ment only. The intervention group received vertebral artery orifice angioplasty and stenting ＋ identical drug treatment to the control group. At 13 days after treatment, the Dizziness Handicap Inventory score was compared between the intervention and control groups. Cerebellar function remodeling was observed between the two groups using blood oxygen level-dependent functional magnetic resonance imaging. The improvement in dizziness handicap and cerebellar function was more obvious in the intervention group than in the control group. Interventional therapy for severe vertebral artery orifice stenosis may effectively promote cerebellar function remodeling and exert neuroprotective effects.

Changes in a cerebellar peduncle lesion in a patient with Dandy-Walker malformation A diffusion tensor imaging study

We report a patient with severe ataxia due to Dandy-Walker malformation, who showed functional recovery over 10 months corresponding to a change in a cerebellar peduncle lesion. A 20-month-old female patient who was diagnosed with Dandy-Walker syndrome and six age- and sex-matched healthy control subjects were enrolled. The superior cerebellar peduncle, the middle cerebellar peduncle, and the inferior cerebellar peduncle were evaluated using fractional anisotropy and the apparent diffusion coefficient. The patients＇ functional ambulation category was 0 at the initial visit, but improved to 2 at the follow-up evaluation, and Berg＇s balance scale score also improved from 0 to 7. Initial diffusion tensor tractography revealed that the inferior cerebellar peduncle was not detected, that the fractional anisotropy of the superior cerebellar peduncle and middle cerebellar peduncle decreased by two standard deviations below, and that the apparent diffusion coefficient increased by two standard deviations over normal control values. However, on follow-up diffusion tensor tractography, both inferior cerebellar peduncles could be detected, and the fractional anisotropy of superior cerebellar peduncle increased to within two standard deviations of normal controls. The functional improvement in this patient appeared to correspond to changes in these cerebellar peduncles. We believe that evaluating cerebellar peduncles using diffusion tensor imaging is useful in cases when a cerebellar peduncle lesion is suspected.

Recovery of cerebellar peduncle injury in a patient with a cerebellar tumor: validation by diffusion tensor tractography

The cerebellum has a complex network and relates to various clinical functions including ataxia, gait disturbance, hearing and vision, cognition and affective control. Cerebellar peduncles are the structure connecting the cerebellum to the brain stem and the cerebrum. There exist three cerebellar peduncles. The superior cerebellar peduncle （SCP） involves vestibular sense and proprio- ception connecting to the thalamocortical pathway. The middle cerebellar peduncle （MCP） is the largest structure among the three cerebellar peduncles conveying impulses from the cerebral cortex to the cerebellum through corticopontocerebellar tract.

Anti-Yo antibody-positive paraneoplastic cerebellar degeneration in a patient with possible cholangiocarcinoma:A case report and review of the literature

Paraneoplastic cerebellar degeneration(PCD),which is rare in clinical practice,is closely related to autoimmunity.Cases positive for anti-Yo antibodies(anti-Purkinje cytoplasmic antibody 1)are the main subtype of PCD.PCD is subacute cerebellar degeneration,and while it progresses over weeks to months,its resultant deficits last much longer.Cancer patients with anti-Yo antibody-positive PCD are very rare.Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients.CASE SUMMARY A 61-year-old woman presented with sudden vertigo,nausea,and vomiting for approximately 10 d.The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk.Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive,positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes,and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct,which strengthens the hypothesis of paraneoplastic origin.Intravenous immunoglobulin(IVIg)0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated,which was reduced to 80 mg for 3 d and then to 40 mg for 7 d.After treatment with IVIg and a steroid,the patient's vertigo and ataxia alleviated.CONCLUSION The patient's vertigo and ataxia alleviated after treatment,suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.

Sudden deafness as a prodrome of cerebellar artery infarction:Three case reports

BACKGROUND To summarize the clinical characteristics of acute cerebral infarction(ACI)in patients with sudden deafness(SD)as the first symptom,improve the awareness of the disease,and help diagnosis and treatment.CASE SUMMARY From 2019 to 2020,three patients with ACI with SD as the first symptom were admitted to our hospital.Pure tone audiometry,head magnetic resonance imaging(MRI),vertebral artery and carotid artery B-ultrasound,head and neck computed tomography angiography,and other examinations were performed.Following the treatment of SD,hearing and dizziness were not significantly improved.Then,the patients developed symptoms of related cranial nerve injury,and brain MRI showed cerebral infarction in the cerebellopontine angle area.All three cases were transferred to the neurology department for relevant conservative treatment.CONCLUSION Patients with ACI with SD as the first symptom usually attend the otolaryngology clinic.Here a diagnosis of SD,which is based on an audiological examination,is made and the corresponding treatment is administered.To reduce the misdiagnosis of this disease,close attention should be paid to the changes in the patient's clinical symptoms and related auxiliary examinations should be performed,such as brain MRI and cerebrovascular imaging.Otolaryngologists should pay attention to the type and severity of hearing loss,the accompanying symptoms,age,high-risk factors for cerebral infarction,and related cranial nerve symptoms in patients with SD.If the patient's early brain MRI does not show abnormalities,monitoring remains essential.The head MRI should be analyzed quickly based on the changes in the symptoms of the patient,to make an accurate diagnosis and provide the timely and correct treatment for the patients.

Diffusion tensor imaging for measuring recovery from cerebellar peduncle injury due to intracerebral hemorrhage: A case report

Diffusion tensor tractography （DTT） in diffusion tensor imaging （DTI） examination allows for the three-dimensional visualization of cerebellar peduncles. The present case-control study analyzed the relationship between functional recovery of intracerebral hematoma patient and cerebellar peduncle injury, as detected by DTI. The enrolled patient could not sit at 3 weeks after onset, but was able to walk independently and perform most daily activities after 4 months. The 3-week DTT images revealed that all six cerebellar peduncles were compressed by the hematoma, posterior portions of all three left cerebellar peduncles were shortened, and the left middle cerebellar peduncle was interrupted in the mid-portion. The 4-week DTT images showed that all compressed cerebellar peduncles were ameliorated, although injured posterior portions of the three left cerebellar peduncles did not recover. The fractional anisotropy value of the right inferior cerebellar peduncle increased from two standard deviations below the normal control value to within two standard deviations of the normal control value. These findings suggested that functional recovery was primarily due to decompression of compressed cerebellar peduncles, and not to recovery of injured cerebellar peduncles. DTI evaluations of cerebellar peduncles could be helpful when cerebellar peduncle injury is suspected.

Development of the cerebellar cortex in the mouse

The cerebellum is a highly conserved structure in the central nervous system of vertebrates, and is involved in the coordination of voluntary motor behavior. Supporting this function, the cerebellar cortex presents a layered structure which requires precise spatial and temporal coordination of proliferation, migration, differentiation, and apoptosis events. The formation of the layered structure in the developing cerebellum remains unclear. The present study investigated the development of the cerebellar cortex. The results demonstrate that the primordium of the cerebellum comprises the ependymal, mantle, and marginal layers at embryonic day 12 （E12）. Subsequently, the laminated cerebellar cortex undergoes cell proliferation, differentiation, and migration, and at about postnatal day 0 （P0）, the cerebellar cortex presents an external granular layer, a molecular layer, a Purkinje layer, and an internal granular layer. The external granular layer is thickest at P6/7 and disappears at P20. From P0 to P30, the internal granular cells and the Purkinje cells gradually differentiate and develop until maturity. Apoptotic neurons are evident in the layered structure in the developing cerebellar cortex. The external granular layer disappears gradually because of cell migration and apoptosis. The cells of the other layers primarily undergo differentiation, development, and apoptosis.

Nitric oxide promotes survival of cerebellar granule neurons cultured in vitro through the Akt pathway

In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyI-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1 -one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered, caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.

Ethanol exposed maturing rat cerebellar granule cells show impaired energy metabolism and increased cell death after oxygen-glucose deprivation

Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.

Cerebellar Degeneration-related Antigen 1 Is Ubiquitously Expressed in Human Epidermis and Dermis

Cerebellar degeneration-related antigen 1(CDR1)was described to be expressed in the nervous system and in different types of cancer tissues.In the present study,we demonstrate that CDR1 is in addition ubiquitously expressed in human epidermis,dermis and isolated skin cells.Both CDR1 mRNA and protein were detected in human skin-derived mast cells,melanocytes,fibroblasts and keratinocytes,suggesting that CDR1 does not have a neuron-specific function.

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Effects of Maternal Marginal Iodine Deficiency on Interactions between Cerebellar Bergmann Glia Cells and Purkinje Cells in Rat Offspring

Iodine deficiency （ID） during early pregnancy has an adverse effect on children＇s psychomotor and motor function but the mechanism has not been clarified. Therefore, our aim was to study the effect of maternal marginal ID on cerebellar neurodevelopment and the underlying mechanism. After obtaining marginal ID rats, we examined interactions between Bergmann gila cells （BGs） and Purkinje cells （PCs） using immunofluorescence and expression of the glutamate transporter and receptor by western blot. Our results showed that marginal ID reduced the number of contacted points between BGs and PCs,