ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy.

The aim of this document is to provide evidence-based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representatives. The development of these recommendations is based on a systematic review of studies on the treatment of depression in adults with epilepsy, and a formal adaptation process of existing guidelines and recommendations of treatment of depression outside epilepsy using the ADAPTE process. The systematic review identified 11 studies on drug treatments (788 participants, class of evidence III and IV); 13 studies on psychological treatments (998 participants, class of evidence II, III and IV); and 2 studies comparing sertraline with cognitive behavioral therapy (CBT; 155 participants, class of evidence I and IV). The ADAPTE process identified the World Federation of Societies of Biological Psychiatry guidelines for the biological treatment of unipolar depression as the starting point for the adaptation process. This document focuses on first-line drug treatment, inadequate response to first-line antidepressant treatment, and duration of such treatment and augmentation strategies within the broader context of electroconvulsive therapy, psychological, and other treatments. For mild depressive episodes, psychological interventions are first-line treatments, and where medication is used, selective serotonin reuptake inhibitors (SSRIs) are first-choice medications (Level B). SSRIs remain the first-choice medications (Level B) for moderate to severe depressive episodes; however, in patients who are partially or non-responding to first-line treatment, switching to venlafaxine appears legitimate (Level C). Antidepressant treatment should be maintained for at least 6 months following remission from a first depressive episode but it should be prolonged to 9 months in patients with a history of previous episodes and should continue even longer in severe depression or in cases of residual symptomatology until such symptoms have subsided.

Serotonergic therapy in epilepsy.

PURPOSE OF REVIEW: The serotonergic system is implicated in multiple aspects of epilepsy, including seizure susceptibility, sudden unexpected death in epilepsy (SUDEP), and comorbid depression. Despite the complexity of serotonin's effects on various neuronal networks, ongoing research provides considerable insight into the role of serotonin in human epilepsy. This review explores the potential roles of serotonergic therapies to improve clinical outcomes in epilepsy. RECENT FINDINGS: In recent decades, research has markedly increased our knowledge of the diverse effects of serotonin on brain function. Animal models of epilepsy have identified the influence of serotonin on seizure threshold in specific brain regions, serotoninergic augmentation's protective effects on terminal apnea and mortality in SUDEP, and mechanisms underlying behavioral improvement in some models of comorbid depression. Human clinical studies are largely consistent with animal data but the translation into definitive treatment decisions has moved less rapidly. SUMMARY: Evidence for serotonergic therapy is promising for improvement in seizure control and prevention of SUDEP. For some epilepsies, such as Dravet syndrome, basic research on serotonin receptor agonists has translated into a positive clinical trial for fenfluramine. The cumulative results of safety and efficacy studies support the routine use of SSRIs for comorbid depression in epilepsy.

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

BACKGROUND: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. METHODS: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. RESULTS: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ±â€¯19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ±â€¯7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. CONCLUSION: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.

Atypical adult-onset subacute sclerosing panencephalitis.

Although subacute sclerosing panencephalitis is almost exclusively a childhood disease, it can occur in adults as well. We present an atypical case of adult-onset subacute sclerosing panencephalitis. The disease was characterized by prolonged insidious course followed by accelerated and aggressive phase, atypical EEG findings, and absence of myoclonic jerks. The diagnostic and treatment-related pitfalls are discussed.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Differences in emotional stimuli processing in subjects with MTLE with and without depression.

In healthy people, a preference in attention maintenance and memory for words with emotional valence comparing to neutral words has been shown. The pattern of emotional stimuli processing may be different in people with mesial temporal lobe epilepsy (MTLE) and it may be sensitive to the presence of depressive symptoms. In order to explore these possibilities, we applied the emotional spatial cueing attentional task and the free recall memory task to participants (N=39) with MTLE and compared them with healthy controls. We hypothesized that the pattern of maintaining attention and remembering emotional words is different in people with MTLE. Current literature indicates that this pattern will change from positive bias in the controls, though no emotional bias in the participants with MTLE without depression (MTLE-d), and in this work we examined this pattern in the participants with MTLE with depressive symptoms (MTLE+d). Our results show that in both attention and memory, control subjects exhibit positive emotional bias, the subjects with MTLE-d show nonemotional bias and the subjects with MTLE+d have bias away from positive words. Participants with MTLE+d maintained attention for positive words shorter than others. Participants with MTLE+d had worse recall for positive words than the participants with MTLE-d and for all words when compared to controls. We found that faster attention disengagement from positive words and worse memory for positive words is associated with elevated levels of depressive symptoms.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe.

OBJECTIVE: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. METHODS: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations. RESULTS: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used. SIGNIFICANCE: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods.

Severe hippocampal atrophy is not associated with depression in temporal lobe epilepsy.

Depression in temporal lobe epilepsy (TLE) is common, is a strong predictor of subjective disability, and may have unique pathophysiological characteristics. Previous studies showed that reduced hippocampal volume is associated with significant depressive symptoms in patients with TLE. We utilized regions of interest analysis of high-resolution brain MRI and a reliable and valid measure of depressive symptoms to evaluate 28 consecutive adult subjects with video-EEG-confirmed TLE. Regions of interest were based on prior human and animal studies of mood and behavioral dysfunction. Forty-three percent of the entire group had significant symptoms of depression, defined by a Beck Depression Inventory (BDI) score of greater than 15. Total hippocampal volumes were significantly smaller in the group with BDI<15, (p<0.007). None of the subjects in the quartile with the smallest left hippocampal volume had a BDI score greater than 15 compared with 57% of the subjects in the upper three quartiles (p<0.008). No other limbic brain structures (amygdala, subcallosal gyrus, subgenual gyrus, gyrus rectus), or total cerebral volume were associated with depressive symptoms. Adequate hippocampal integrity may be necessary to maintain depression symptoms in mesial temporal lobe epilepsy. This finding also supports the possibility of a unique mechanism for depression in mesial temporal lobe epilepsy, such as hyperexcitable neuronal influence on the limbic network.

Epilepsy, cognition, and neuropsychiatry (Epilepsy, Brain, and Mind, part 2).

Epilepsy is, of course, not one disease but rather a huge number of disorders that can present with seizures. In common, they all reflect brain dysfunction. Moreover, they can affect the mind and, of course, behavior. While animals too may suffer from epilepsy, as far as we know, the electrical discharges are less likely to affect the mind and behavior, which is not surprising. While the epileptic seizures themselves are episodic, the mental and behavioral changes continue, in many cases, interictally. The episodic mental and behavioral manifestations are more dramatic, while the interictal ones are easier to study with anatomical and functional studies. The following extended summaries complement those presented in Part 1.

Suicidality in Epilepsy: Does It Share Common Pathogenic Mechanisms with Epilepsy?

Suicidality presents a major global health concern and its association with epilepsy has been suggested. The body of evidence is growing due to targeted epidemiological studies, genetic findings, and neuroimaging data, use of specific neuropsychiatric inventories, neuropsychological tests, and metabolic and immunological studies.Suicide tendencies and psychiatric comorbidity such as depression are not uncommon in chronic diseases, especially in epilepsy. Suicide is an important cause of death in epilepsy, and is usually underestimated. Persons with epilepsy have higher risk for suicide than healthy controls. It appears that some epilepsy types have stronger tendencies for suicide, in particular temporal lobe epilepsy. The suicidal risk factors in persons with epilepsy include difficult to treat epilepsies, onset of epilepsy at an earlier age, and comorbid depression.This clinical evidence is mostly based on observational studies in which we found an increased risk of suicidal ideation, suicidal attempts, and completed suicides in persons with epilepsy. However, we lack prospective and longitudinal studies on suicide in epilepsy. In this chapter we will examine recent research in neurobiological mechanisms between suicidality and epilepsy, and comorbid depression.

Suicidality and epilepsy: a neuropsychobiological perspective.

People with epilepsy (PWE) are at increased risk of experiencing suicidal ideation, displaying suicidal behavior, and committing suicide than the general population. The relationship between suicidality and epilepsy is complex and multifactorial in which operant pathogenic mechanisms include epilepsy-related variables, personal and familial psychiatric history, and iatrogenic effects. Furthermore, a bidirectional relationship between suicidality and epilepsy has suggested the existence of common neurobiological pathogenic mechanisms operant in both conditions and including disturbances of several neurotransmitters, in particular, serotonin (5HT), norepinephrine (NE), glutamate (GTE), and γ-aminobutyric acid (GABA), and disturbances of the hypothalamic-pituitary-adrenal axis (HPAA), which, in turn, can result in abnormal secretion of some of these neurotransmitters. The purpose of this article is to review these common neurobiological pathogenic mechanisms.

Recall and Self-Relevance of Emotional Words Predict Subjective Self-Evaluation of Cognition in Patients with MTLE with or without Depressive Symptoms.

We examined whether word processing is associated with subjective self-evaluation of cognition in patients with mesial temporal lobe epilepsy (MTLE) as a function of their depressive symptoms. MTLE patients with (MTLE +d, N = 28) or without (MTLE -d, N = 11) depression were compared to pair-matched healthy control participants on free recall and self-relevance ratings of emotionally valenced words. Correlation and hierarchical analyses were conducted to investigate whether the subjective self-evaluation of cognition in MTLE patients is predicted by the negative emotional bias reflected in task performance. MTLE +d patients endorsed as self-relevant fewer positive words and more negative words than the MTLE -d patients and healthy participants. They also self-evaluated their cognition poorer than the MTLE -d patients. Analyses indicated that recall and self-endorsement of emotional words predicted both self-evaluation of cognition as well as epilepsy duration. Our findings indicate that negative self-relevance emotional bias is observed in MTLE patients and is predictive of subjective self-evaluation of cognition. Application of brief behavioral tasks probing emotional functions could be valuable for clinical research and practice in the patients with MTLE.

EEG in fitness to drive evaluations in people with epilepsy - Considerable variations across Europe.

PURPOSE: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. METHODS: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the E-pilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. RESULTS: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. CONCLUSION: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.

Prevalence of mood dysfunction in epilepsy patients in Croatia.

Fifty consecutive and consenting epilepsy patients from the Zagreb Epilepsy Center were examined for the presence of depressive symptoms using the Beck Depression Inventory (BDI). This questionnaire has been previously validated for use in the Croatian population. Mean age of the patients was 30.8 +/- 13.5 years, 60.4% were females. Majority of them were employed (72.9%) and single (62.5%), and 35.4% had a university degree. Most of them had complex partial seizures (n=40, 80%), and 6 (12%) were diagnosed with idiopathic generalized epilepsy. Assessment with the BDI showed that 33.3% of patients had recent depressive symptoms: 6.3% had mild depressive symptoms, 8.4% moderate and 18.6% severe depressive symptoms. Three patients (6.4%) attempted suicide in the past, two of them had current suicidal ideation, and all of them were severely depressed. This is the first and preliminary study assessing mood dysfunction in epilepsy patients in Croatia. Increased prevalence of depression in epilepsy patients suggests specific approach and need for early treatment.

[Association of epilepsy and headache from the patient perspective]. / Povezanost epilepsija i glavobolje iz perspektive bolesnika.

Headache occurs more frequently in patients with epilepsy as compared to the general population. Current studies in patients with epilepsy and migraine show that this increased frequency is independent of the seizure type, etiology or age at onset. People with epilepsy are 2.4 times more likely to be diagnosed with migraine. In our study, we evaluated patients' attitudes toward comorbidity of epilepsy and all headache types. Study results showed a significant number of patients to have experienced headaches after being diagnosed with epilepsy, and some of them assumed it was a side effect of their antiepileptic drug. Based on these data, we propose a more detailed assessment of the history of epilepsy including questions on headache, and offer the epilepsy patient a newer antiepileptic drug. In this way, we can significantly decrease the comorbidity of these two neurologic disorders and improve the quality of life in epilepsy patients.

Nonverbal Memory Capacity in Persons with Epilepsy Is Associated with Depression Rather than Anxiety.

Epilepsy is characterized by repeated epileptic seizures, which are manifested in various ways and depend on the location and size of foci in the brain. Long-term seizures with secondary generalization can cause memory problems. Numerous studies demonstrate the connection of memory damage and lateralization in medial temporal lobe epilepsy (TLE). However, the results were not always consistent with the material-specific memory model. A possible explanation for these inconsistent data is the insufficient control of psychological variables that can affect memory. In most of the previous studies in persons with epilepsy, they were not controlled for their emotional states such as anxiety and depression. We used the Rey Complex Figure Test (RCFT) as a measure of visual memory, Beck's depression inventory as a measure of depressive symptoms, and the State-Trait Anxiety Inventory as a measure of anxiety in 57 consecutive participants. Our aim was to investigate whether there is difference in visual memory with respect to the left and right TLE, and whether the participants of different gender with higher anxiety and depression rates would achieve different results on visual memory. Persons with lower levels of depression achieved better scores in the Immediate and Delayed recall subtests of the RCFT. We also explored the potential gender differences. Testing differences between the persons with higher and lower anxiety levels did not reveal any significant differences in any of the measures tested.

Tolosa-Hunt Syndrome - Case Report.

This case report presents a patient diagnosed with Tolosa-Hunt syndrome (THS) after an extensive neuro-diagnostic and neuroimaging evaluation. Diagnostic work-up included thorough physical and neurological examination, complete laboratory serum assessments, neuroendocrine and immunohistochemistry analysis, cerebrospinal fluid analysis, neurophysiology assessment, ophthalmologist examination and neuroimaging. Th e most important diagnostic tool in deriving the diagnosis of THS was neuroimaging evaluation that included baseline and follow-up cranial contrast enhanced magnetic resonance imaging (MRI). Baseline cranial contrast enhanced MRI detected a nonspecific inflammatory granulomatous lesion in the right cavernous sinus extending basally towards the right trigeminal cave (Meckel's cave) and anteriorly towards the apex of the right orbit. Systemic intravenous high-dose corticosteroid therapy was administered for 3 consecutive days and then tapered down to lower oral steroid doses. Following therapy, the patient experienced complete regression of symptoms. Follow-up cranial contrast enhanced MRI showed significant regression of inflammatory lesion in the area of right cavernous sinus, thus verifying the efficacy of the treatment applied. This paper shows that an extensive diagnostic schedule for THS must be conducted prior to therapeutic treatment, for the possibility of alternative diagnosis. Patients suspected of having THS require careful evaluation, appropriate treatment, and follow-up.

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

PURPOSE: The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. METHOD: A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. RESULTS: Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. CONCLUSION: This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe.

THE ROLE OF TILT-TABLE TEST IN DIFFERENTIAL DIAGNOSIS OF UNEXPLAINED SYNCOPE.

The aim of this retrospective study (February 2012-September 2014) was to assess the role of head-up tilt-table test in patients with unexplained syncope. It was performed on 235 patients at Clinical Department of Cardiology, Sestre milosrdnice University Hospital Center. Patients were classified according to test indications: group A (convulsive syncope, n = 30), group B (suspected vasovagal syncope, n = 180), and group C (paroxysmal vertigo, n = 25). The groups were analyzed and compared according to demographic data (age and gender), referral specialist (cardiologist, neurologist, and others), and test results (positive/negative) with specific response (cardioinhibitory, vasodepressor, or mixed). Groups A and B were referred most frequently by neurologists and cardiologists (p < 0.05). The test was positive in 34 (14.5%) of all evaluated patients (5 in group A and 29 in group B), of which 13 (38.2%) had cardioinhibitory, 11 (32.4%) mixed and 10 (29.4%) vasodepressor response. In the cardioinhibitory subgroup, three patients (23.1%, 2 males/1 female, mean age 28.5 years) with normal electroencephalography were on antiepileptics. During head-up tilt-table testing, they had bradycardia (heart rate 30.0 ± 5.0 beats/min) and prolonged asystole (13.7 ± 11.0 seconds) with development of typical convulsions. These three subjects got a permanent pacemaker (atrial/ventricular stimulation, heart rate control) and anticonvulsive therapy was slowly withdrawn with no syncope recurrence during 24-month follow up. In conclusion, head-up tilt-table test has an important role in the evaluation of patients with unexplained syncope and in differential diagnosis of vasovagal syncope. The indication for pacemaker implantation, strictly following the European Society of Cardiology guidelines, proved to be effective in preventing syncope relapses in patients with cardioinhibitory convulsive syncope.

[Occult papillary carcinoma of the thyroid gland with unusual neurologic symptoms]. / Okultni papilarni karcinom stitne zlijezde s neobicnim neuroloskim simptomima.

We present a patient who had progressive cognitive decline and Jackson epileptic seizures and CT scan of nonspecific multiple cortical lesions. Post mortem examination revealed multiple cortical metastases of the brain and primary occult papillary carcinoma of the thyroid gland. Solitary metastases of the left kidney and pulmonary lymphangitic spread were also present. Multiple cortical metastases of the brain from primary occult papillary carcinoma of the thyroid gland with such neurological symptoms have not been reported previously.