Minor Neurological Symptoms Research Articles

Subacute parkinsonism induced by immune checkpoint inhibitors

Abstract Immune checkpoint inhibitors can trigger immune-related side effects, and while neurological involvement is rare, it can be serious. A woman with treatment-refractory intestinal T-cell lymphoma was initiated pembrolizumab and developed a daily fever and parkinsonian syndrome 2 weeks later. The investigation revealed only mild slowing of the background activity on electroencephalogram and slightly elevated cell count and protein levels in her cerebrospinal fluid. Immunotherapy was discontinued, and the patient recovered after 5 days of methylprednisolone. Minor neurological symptoms recurred after the rechallenge with pembrolizumab. Subacute parkinsonian syndromes should be considered a potential neurological event related to immune checkpoint inhibitors.

Acute Basilar Artery Tip Thrombosis Presenting as Basilar-Subclavian Steal Phenomenon on Transcranial Doppler

Acute basilar artery (BA) occlusion is a key etiology of devastating posterior circulation stroke, unless recanalization is performed early. Recanalization therapy is determined synthetically based on symptom onset time, stroke severity, and brain imaging. Herein, we report the case of a 72-year-old male patient presenting with minor neurological symptoms, but with thrombotic occlusion at the BA tip. Transcranial Doppler (TCD) showed systolic flow reversal along the vertebrobasilar arteries, and the patient benefited from endovascular thrombectomy. This case highlights the critical role of TCD in identifying hemodynamic insufficiency and determining the implementation of endovascular interventions to mitigate stroke progression.

Intracranial meningioma: an unusual silent killer—about two cases report and a literature review

BackgroundMeningiomas are common benign intracranial tumors, accounting for 1/3 of all primary intracranial neoplasms, and hence, are not considered the chief cause of death when encountered incidentally during autopsy. These tumors are usually slow-growing, and the clinical course may be asymptomatic to the point of acute complications. Sudden unexpected deaths due to meningiomas are exceptional and rarely reported in the literature.In the present report, we describe two autopsy cases of sudden unexpected death due to meningiomas and we discuss the mechanism of death.Case presentationTwo apparently healthy men were discovered dead in their home. A judicial autopsy was ordered. At dissection, a pedunculated firm mass, attached to the dura was found in both cases. Tumors were located in the anterior and middle fossa. The remaining organs were congestive without any abnormality. A microscopic examination confirmed the diagnosis of meningiomas. Postmortem toxicology analysis was negative. Forensic pathologists concluded to sudden unexpected death due to intracranial meningioma.ConclusionsThese cases illustrate the possibility of meningioma remaining silent till acute complication and fatal outcome. Therefore, clinicians must bear in mind the possibility, albeit extremely rare, of sudden unexpected death in cases of undiagnosed intracranial meningiomas, as documented in the present report. Thus, we emphasize the value of promptly and thoroughly investigating even seemingly minor neurological symptoms, such as headaches or acute epileptic seizures, in adults. We also stress the importance of the early detection and appropriate management of brain tumors in fatal outcome prevention, and we highlight the role of the post-mortem examination to detect such a fatal complication.

Safety Aspects and Procedural Characteristics of Ambulatory Diagnostic Cerebral Catheter Angiography.

Diagnostic cerebral catheter angiography is used to assess avariety of neurovascular pathologies especially in patients before and after endovascular neurointerventional treatment. In many centers diagnostic cerebral angiographies are performed with the patient staying for one night in the hospital because there are not yet sufficient data on the safety of ambulatory cerebral angiography. At the same time hospitals face agrowing demand to perform ambulatory medical procedures. A total of 426 ambulatory diagnostic cerebral angiographies were retrospectively analyzed. Technical details of the angiographies were analyzed to identify procedural risk factors. Out of 426 patients 14 (3.3%) had some form of complication, 3 developed minor transient neurological symptoms, 1 patient developed Quincke's edema probably as an adverse reaction to contrast agent, 1 patient had an asymptomatic carotid dissection and 1 had afall of unknown etiology. Of the 14complications 8 were puncture site complications with 1 re-bleeding, 1 dissection, and 6 minor complications, 421 punctures were femoral, 3 radial and 2 brachial. Out of 333 patients with magnetic resonance imaging (MRI) after angiography 21 showed focal diffusion-weighted imaging (DWI) lesions but none of these lesions were symptomatic. The rate of DWI lesions was significantly higher in selectively angiography territories than in other territories. The use of aSimmons 2catheter significantly increased the rate of DWI lesions (p = 0.047), whereas 3D rotational angiography did not (p = 0.55). The rate of DWI lesions per selectively accessed vessel was 4.6% with ahigher rate in the anterior than in the posterior circulation. Diagnostic cerebral catheter angiography can be safely performed in an ambulatory setting.

Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes.

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or "long COVID"), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

Background:The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke.Methods:Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment.Results:Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%–42%]); possible 26 out of 151 (17% [12%–24%]); and uncertain 9 out of 43, (20% [10%–36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%–53%]); migraine aura 4 out of 38 (11% [3%–25%]); non-TIA focal symptoms 16 out of 99 (16% [10%–25%]); and no focal features 1 out of 29 (3% [0%–18%]). After MRI, a further 14 (5% [95% CI, 3–8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3–62]; P<0.0001).Conclusions:MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

Exposure to immediate-release tramadol in children 6 years and under – a nationwide French poison control center study

Introduction Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. Results We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p < .0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p < .0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p < .001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Conclusions Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures.

Abstract P257: Cost-Effectiveness of Advanced Neuroimaging for Transient &amp; Minor Neurological Events in the Emergency Department

Background: Accurate diagnosis of patients with transient or minor neurological events is challenging with non-trivial rates of Emergency Department (ED) misdiagnosis reported. Recent studies suggest that advanced neuroimaging can improve diagnostic accuracy in presumed low-risk patients, but a cost-effective ED diagnostic evaluation strategy remains uncertain. We therefore evaluate two strategies designed to determine which patients with low-risk transient and minor neurological symptoms can be directly discharged from the ED. Methods: We constructed a decision-analytic model to evaluate two ED-based diagnostic evaluation strategies for patients with presumed low-risk transient or minor neurological symptoms: (1) obtain advanced neuroimaging (MRI brain and MRA head and neck) in the ED on every patient or (2) current ED standard of care of clinical evaluation and basic neuroimaging. The main probability variables were: proportion of patients with true ischemic events, specificity and sensitivity of each evaluation strategy, recurrent stroke rate, and direct healthcare costs. We calculated incremental cost-effectiveness ratios (ICER) and performed threshold analyses to evaluate diagnostic test parameters. Cost-effectiveness was defined as willingness to pay (WTP) &lt;$100,000 USD per quality adjusted life year (QALY) gained. Results: Our primary and sensitivity analyses found that the advanced neuroimaging strategy more cost-effective than ED standard of care, the latter of which has an ICER exceeding the WTP threshold. The total cost of the advanced neuroimaging strategy was $3,210 with an effectiveness of 0.9397 whereas the total cost of the standard ED strategy was $4,338 with an effectiveness of 0.9399 in the primary model. Using threshold analyses, we found that potential superior diagnostic approaches to the advanced neuroimaging strategy would have to be &gt;92% specific, &gt;70% sensitive, and cost less than or equal to the standard of care strategy. Conclusion: In our decision-analytic model, obtaining advanced neuroimaging on all patients presenting with low-risk transient and minor neurological symptoms was the more cost-effective strategy as compared to current practice.

Unintentional exposure to pregabalin in ≤6-year-old children: a nationwide French Poison Control Center study

Introduction In France, pregabalin is widely prescribed in adults but still not approved for children. We aimed to investigate the incidence of pregabalin exposure in ≤6-year-old children, to describe the characteristics and outcome of ingestions involving pregabalin alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of pregabalin exposures in ≤6-year-old children, collected by the French Poison Control Centers in 2004–2019. The incidence was estimated using pregabalin prescription data from the Health Improvement Network database (the French version of THIN). The poison severity score (PSS) was used to grade severity. Results We found 313 unintentional immediate-release pregabalin ingestions in ≤6-year-old children. The number of cases per 100,000 pregabalin-treated adults increased over time (p < 0.001). One hundred twenty-six cases involving pregabalin alone (age, 2 years [1.6–3.0] (median [25th–75th percentiles]); median ingested dose 6.4 mg/kg [3.6–10.9]) were analyzed. No child presented an underlying neurological/cardiac disease and/or took concomitant medications. Most of the children (77%) remained asymptomatic (PSS0) while 21% and 2% developed minor (PSS1) or moderate (PSS2) neurological symptoms, respectively. No severe complications/fatalities were reported. All symptomatic children recovered within 24 h. The ingested pregabalin dose was positively correlated with PSS (p < 0.0001). Using a ROC curve approach (area under the curve, 0.85; p < 0.001), ingestion of ≥19.4 mg/kg pregabalin was appropriate to recommend hospital referral (sensitivity, 39% [95% confidence interval (95% CI), 24–56], specificity, 100% [95% CI, 96–100], predictive positive value, 100% [95% CI, 64–100], and negative predictive value, 85% [95% CI, 82–89]). Symptomatic children who ingested <19.4 mg/kg pregabalin developed minor symptoms. Conclusion Despite increasing prescriptions in adults in France, unintentional pregabalin ingestions in ≤6-year-old children remain rare and cause minimal toxicity. Children with no underlying neurological/cardiac disease and concomitant medication ingesting <19.4 mg/kg immediate-release pregabalin alone can be safely observed at home.

MRI Findings After “Minor” Neurological Events

Patients frequently present to us a few days after experiencing minor neurological symptoms that might (or might not) represent brain ischemia. In this

Sex Differences in Presentation and Outcome After an Acute Transient or Minor Neurologic Event

Sex differences have been described in the presentation, care, and outcomes among people with acute ischemic strokes, but these differences are less understood for minor ischemic cerebrovascular events. The present study hypothesized that, compared with men, women are more likely to report nonfocal symptoms and to receive a stroke mimic diagnosis. To evaluate sex differences in the symptoms, diagnoses, and outcomes of patients with acute transient or minor neurologic events. This prospective cohort study of patients with minor ischemic cerebrovascular events or stroke mimics enrolled at multicenter academic emergency departments in Canada between December 2013 and March 2017 and followed up for 90 days is a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment). In total, 1729 consecutive consenting patients with acute transient or minor neurologic symptoms were referred for neurologic evaluation; 66 patients were excluded for protocol violation (n = 46) or diagnosis of transient global amnesia (n = 20). The main exposure was female or male sex. The main outcome was the clinical diagnosis (cerebral ischemia vs stroke mimic). Secondary outcomes were 90-day stroke recurrence and 90-day composite outcome of stroke, myocardial infarction, or death. The association between presenting symptoms (focal vs nonfocal) and clinical diagnosis was also assessed. Research hypotheses were formulated after data collection. Of 1648 patients included, 770 (46.7%) were women, the median (interquartile range) age was 70 (59-80) years, 1509 patients (91.6%) underwent brain magnetic resonance imaging, and 1582 patients (96.0%) completed the 90-day follow-up. Women (522 of 770 [67.8%]) were less likely than men (674 of 878 [76.8%]) to receive a diagnosis of cerebral ischemia (adjusted risk ratio [aRR], 0.88; 95% CI, 0.82-0.95), but the 90-day stroke recurrence outcome (aRR, 0.90; 95% CI, 0.48-1.66) and 90-day composite outcome (aRR, 0.86; 95% CI, 0.54-1.32) were similar for men and women. No significant sex differences were found for presenting symptoms. Compared with patients with no focal neurologic symptoms, those with focal and nonfocal symptoms were more likely to receive a diagnosis of cerebral ischemia (aRR, 1.28; 95% CI, 1.15-1.39), but the risk was highest among patients with focal symptoms only (aRR, 1.45; 95% CI, 1.34-1.53). Sex did not modify these associations. The results of the present study suggest that, despite similar presenting symptoms among men and women, women may be more likely to receive a diagnosis of stroke mimic, but they may not have a lower risk than men of subsequent vascular events, indicating potentially missed opportunities for prevention of vascular events among women.

Clinical diagnosis of TIA or minor stroke and prognosis in patients with neurological symptoms: A rapid access clinic cohort.

BackgroundThe long-term risk of stroke or myocardial infarction (MI) in patients with minor neurological symptoms who are not clinically diagnosed with transient ischaemic attack (TIA) or minor stroke is uncertain.MethodsWe used data from a rapid access clinic for patients with suspected TIA or minor stroke and follow-up from four overlapping data sources for a diagnosis of ischaemic or haemorrhagic stroke, MI, major haemorrhage and death. We identified patients with and without a clinical diagnosis of TIA or minor stroke. We estimated hazard ratios of stroke, MI, major haemorrhage and death in early and late time periods.Results5,997 patients were seen from 2005–2013, who were diagnosed with TIA or minor stroke (n = 3604, 60%) or with other diagnoses (n = 2392, 40%). By 5 years the proportion of patients who had a subsequent ischaemic stroke or MI, in patients with a clinical diagnosis of minor stroke or TIA was 19% [95% confidence interval (CI): 17–20%], and in patients with other diagnoses was 10% (95%CI: 8–15%). Patients with clinical diagnosis of TIA or minor stroke had three times the hazard of stroke or MI compared to patients with other diagnoses [hazard ratio (HR)2.83 95%CI:2.13–3.76, adjusted age and sex] by 90 days post-event; however from 90 days to end of follow up, this difference was attenuated (HR 1.52, 95%CI:1.25–1.86). Older patients and those who had a history of vascular disease had a high risk of stroke or MI, whether or not they were diagnosed with minor stroke or TIA.ConclusionsCareful attention to vascular risk factors in patients presenting with transient or minor neurological symptoms not thought to be due to stroke or TIA is justified, particularly those who are older or have a history of vascular disease.

Psychiatric disorders secondary to neurometabolic disorders

Some diseases secondary to inborn errors of metabolism are associated with psychiatric disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Diagnostic accuracy of whole-brain computed tomography perfusion for detection of ischemic stroke in patients with mild neurological symptoms.

Mild and minor acute neurological symptoms may lead to diagnostic uncertainty, resulting in a heterogeneous group of patients with true ischemic events and stroke mimics with a potential for poor outcomes. More than half of ischemic stroke patients present as minor strokes (National Institutes of Health Stroke Scale score <6). Whole-brain computed tomography perfusion can be used as a diagnostic test for minor stroke, offering a potential method of reducing diagnostic uncertainty in these patients. We hypothesize that whole-brain computed tomography perfusion imaging features could accurately predict infarction in patients with minor neurological deficits. This retrospective chart review enrolled consecutive patients suspected of acute ischemic stroke with a National Institutes of Health Stroke Scale score <6, who underwent whole-brain computed tomography perfusion and follow-up diffusion-weighted magnetic resonance imaging at our institution. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for whole-brain computed tomography perfusion, using follow-up diffusion-weighted magnetic resonance imaging as a reference standard. A total of 524 patients (mean age: 67 years; range: 17-96 years; 56% men) met the inclusion criteria. Patients were excluded for non-diagnostic ( n = 25) or missing maps ( n = 8) scans, non-ischemic findings ( n = 7), and lack of follow-up magnetic resonance imaging ( n = 336). The final analysis included 148 patients who underwent diffusion-weighted magnetic resonance imaging. Whole-brain computed tomography perfusion has a sensitivity of 0.57 (95% CI: 0.45-0.69) and a specificity of 0.82 (95% CI: 0.71-0.90). The positive and negative predictive values and positive and negative likelihood ratios were 75%, 67%, 3.09, and 0.53, respectively. Our analysis suggests that although whole-brain computed tomography perfusion may offer some value as an adjunctive test for improving confidence in offering stroke treatment, it is not sufficiently sensitive or specific to accurately predict cerebral infarcts in patients with minor neurological symptoms.

Investigation of distinctive characteristics of children with specific learning disorder and borderline intellectual functioning

Background Borderline intelligence function (BIF) and specific learning disorder (SLD) are common diagnoses in children who are brought up for learning problems and school failure. Objective The aim of our study was to determine whether there were distinctive aspects of cognitive testing routinely used in evaluating SLD and BIF and investigate emotion regulation skills and minor neurologic symptoms. Method Sixty children (30 SLD and 30 BIF) who are currently attending primary school are selected for study. Visual Aural Digit Span Test – Form B, Gessel Figure Drawing Test, Bender Gestalt Visual Motor Perception Test, WISC-R, Emotion Regulation Scale (ERS) and Neurological Evaluation Scale (NES) was administered. Results There was no statistically significant difference between groups in cognitive tests. The emotional regulation ability measured by the emotional regulation subscale was better in the SLD group than the BIF group (p = 0.014). In the NES, sensory integration (p = 0.008), motor coordination (p = 0.047) and other (p < 0.001) subscales showed higher scores in the BIF group. Discussion It has been shown that cognitive tests don’t have distinguishing features in the evaluation of SLD and BIF. Emotion regulation subscale score of ERS and sensory integration, motor coordination, and total scores of NES can be used in both discrimination of groups.

Trastornos psiquiátricos secundarios a enfermedades neurometabólicas

Some diseases secondary to inborn errors of metabolism are associated with psychiatric disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Reelin blood levels as a marker of some types of autistic spectrum disorders (ASD)

Objective: Reelin is a large glycoprotein secreted from specific neurons within the developing brain and encoded by RELN gene. Reelin regulates the signaling pathway of post-mitotic neurons to reach the proper layer of the central nervous system parenchyma, suggesting that deficiencies in the expression of RELN gene could play a role in the genesis of schizophrenia and ASD. Our aim is to find differences in the blood expression of Reelin between ASD patients and controls. Methods: A referral group of 30 ASD patients (27 boys and three girls) (Mean decimal age= 7.84±3.4 SD) were recruited from the neuropaediatric outpatient clinic of a secondary hospital. After meeting the criteria for ASD diagnosis, we invited the families to donate an aliquot from a blood test, required for clinical reasons. Samples were analyzed for plasma Reelin protein levels by Western blots. Other 10 patients (four boys and six girls) (Mean decimal age= 8.5±4.5 SD) suffering from minor neurologic symptoms such as headaches, dizziness, varied paroxysms and who also required a blood analysis (with normal results) accepted to join the study as controls. The data were tabulated and analyzed with the EpiInfo 7.2 statistical package, following the directions of the local ethics committee. Results: Sixteen patients of the ASD group (53.33%) showed Reelin values over the normal range, while only one from the control group did it (10%) being these differences statistically significant (OR=10.3; CI:1.15-91.6). Sixteen boys (56.61%) and one girl (11.11%) of the whole group showed elevated Reelin values near of statistical significance (OR=8.5; CI:0.95-76.6). Conclusion: In our series, patients suffering from ASD are 10 times more likely to present high Reelin blood levels than controls, suggesting the possibility that Reelin blood levels could be a suitable marker of some ASD types, although gender could play the role of a confusing factor.

Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer.

This article presents methods and results of surgery and radiotherapy of brain metastases from non-small cell lung cancer (BMF-NSCLC). Patients with single BMF-NSCLC, with Karnofsky score ≥ 70 and controlled extracranial disease are the best candidates for surgery. Stereotactic radiosurgery (SRS) is recommended in patients with 1–3 BMF-NSCLC below 3–3.5 cm, with minor neurological symptoms, located in parts of the brain not accessible to surgery, with controlled extracranial disease. Whole brain radiotherapy (WBRT) following SRS reduces the risk of local relapse; in selected patients median survival reaches more than 10 months. Whole brain radiotherapy alone is a treatment in patients with multiple metastases, poor performance status, uncontrolled extracranial disease, disqualified from surgery or SRS with median survival 3 to 6 months. There is no doubt that there are patients with BMF-NSCLC who should receive only the best supportive care. There is a debate in the literature on how to select these patients.

Absolute cardiovascular risk and GP decision making in TIA and minor stroke.

Transient ischaemic attacks (TIA) and minor strokes (TIAMS) have the same pathophysiological mechanism as stroke and carry a high risk of recurrent ischaemic events. Diagnosis of TIAMS can be challenging and often occurs in general practice. Absolute cardiovascular risk (ACVR) is recommended as the basis for vascular risk management. Consideration of cardiovascular risk in TIAMS diagnosis has been recommended but its utility is not established. Firstly, to document the ACVR of patients with incident TIAMS and with TIAMS-mimics. Secondly, to evaluate the utility of ACVR calculation in informing the initial diagnosis of TIAMS. The International comparison of Systems of care and patient outcomes in minor Stroke and TIA (InSiST) study is an inception cohort study of patients of 17 Australian general practices presenting as possible TIAMS. An expert panel determines whether participants have had TIAMS or TIAMS-mimics. ACVR was calculated at baseline for each participating patient. In this cross-sectional baseline analysis, ACVR of TIAMS and TIAMS-mimics were compared univariately and, also, when adjusted for age and sex. The diagnostic utility of ACVR was evaluated via receiver operating characteristic (ROC) curves. Of 179 participants, 87 were adjudicated as TIAMS. The presence of motor and speech symptoms and body mass index were associated with a diagnosis of TIAMS. ACVR was associated with TIAMS diagnosis on univariate analysis, but not when age- and sex-adjusted. ACVR did not significantly improve area under ROC curves beyond that of age and sex. In patients presenting with transient or minor neurological symptoms, calculation of ACVR did not improve diagnostic accuracy for TIAMS beyond that of age and sex.

Unravelling the complex MRI pattern in glutaric aciduria type I using statistical models-a cohort study in 180 patients.

Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by inherited deficiency of glutaryl-CoA dehydrogenase and is characterized biochemically by an accumulation of putatively neurotoxic dicarboxylic metabolites. The majority of untreated patients develops a complex movement disorder with predominant dystonia during age 3-36months. Magnetic resonance imaging (MRI) studies have demonstrated striatal and extrastriatal abnormalities. The major aim of this study was to elucidate the complex neuroradiological pattern of patients with GA-I and to associate the MRI findings with the severity of predominant neurological symptoms. In 180 patients, detailed information about the neurological presentation and brain region-specific MRI abnormalities were obtained via a standardized questionnaire. Patients with a movement disorder had more often MRI abnormalities in putamen, caudate, cortex, ventricles and external CSF spaces than patients without or with minor neurological symptoms. Putaminal MRI changes and strongly dilated ventricles were identified as the most reliable predictors of a movement disorder. In contrast, abnormalities in globus pallidus were not clearly associated with a movement disorder. Caudate and putamen as well as cortex, ventricles and external CSF spaces clearly collocalized on a two-dimensional map demonstrating statistical similarity and suggesting the same underlying pathomechanism. This study demonstrates that complex statistical methods are useful to decipher the age-dependent and region-specific MRI patterns of rare neurometabolic diseases and that these methods are helpful to elucidate the clinical relevance of specific MRI findings.