Reversible metronidazole-induced encephalopathy

We report the neuroimaging findings of a case of reversible metronidazole-induced encephalopathy. Magnetic resonance imaging (MRI) demonstrated lesions in highly suggestive locations. Follow-up imaging performed 1 month after cessation of metronidazole therapy demonstrated resolution of imaging findings.     

Defining the phenotype of FHF1 developmental and epileptic encephalopathy

Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1-DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely pathogenic variant p.Gly112Ser. The p.Arg114His variant is associated with an earlier onset and more severe phenotype. One patient carried a chromosomal microduplication involving FHF1. Twelve patients carried a de novo variant, five (29.5%) inherited from parents with gonadic or somatic mosaicism. Seizure onset was between 1 day and 41 months; in 76.5% it was within 30 days. Tonic seizures were the most frequent seizure type. Twelve patients (70.6%) had drug-resistant epilepsy, 14 (82.3%) intellectual disability, and 11 (64.7%) behavioral disturbances. Brain magnetic resonance imaging (MRI) showed mild cerebral and/or cerebellar atrophy in nine patients (52.9%). Overall, our findings expand and refine the clinical, EEG, and imaging phenotype of patients with FHF1-DEE, which is characterized by early onset epilepsy with tonic seizures, associated with moderate to severe ID and psychiatric features.     

MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia]

A 69-year-old man was referred to our department because of acute onset nausea, vomiting, dysphagia, dysarthria and gait disturbance. He had a 50-day-history of amebic dysentery and had been treated with 1,500 mg metronidazole per day. Neurological examination revealed dysphagia, ataxic speech, ataxia of the left extremities and the trunk, and hyperactive deep tendon reflexes in all extremities. Sensory impairment of all modalities was apparent in a glove and stocking pattern, with mild paresthesia. Brain MRI showed T2 high signal lesions in the bilateral cerebellar dentate nuclei, more markedly on the left. On brain SPECT, obvious low blood perfusion was observed in the left cerebellar hemisphere. These findings well explained the ataxia of the left limbs. One month after discontinuing metronidazole, the cerebellar ataxia, dysphagia and MRI abnormalities completely cleared. Therefore, central nervous system damage induced by metronidazole is considered reversible. In spite of the presence of the MRI lesion in the right dentate nucleus, the patient had no ataxia of the right extremities and there was no hypoperfusion in the right cerebellar hemisphere. Thus, metronidazole does not appear to have a direct neurotoxic effect on the central nervous system. On the other hand, nerve conduction studies showed axonal polyneuropathy, which was not improved one month after cessation of the drug; thus metronidazole seems to exert more damage on peripheral nerves.     

Defining Dyslexia

We argue against defining dyslexia as requiring by definition the presence of demonstrable phonological difficulty, and also against defining it in relation to exclusion criteria. Instead, we suggest that what matters is evaluating any child's set of reading subskills against age-related norms for those subskills. We also argue that in considering the causes of reading difficulty it is essential to distinguish between proximal cause (some abnormality in the information-processing system that the child is using to read) and distal cause (the reason for this system being abnormal). The same proximal cause (e.g. poor phonic knowledge) can be the product of different distal causes in different children (e.g. the distal cause might be constitutional, environmental, or educational).     

Defining mixed depression

BACKGROUND: Mixed depression, i.e. a major depressive episode plus co-occurring manic/hypomanic symptoms, has recently become the focus of research. However, it is still unclear if its definition should be based on specific manic symptoms or on a number/score of manic symptoms. Different definitions may have different diagnostic utility, such as treatment impacts. STUDY AIM: Study aim was to test which definition of mixed depression was more supported, by using, as diagnostic validator, early age at onset on the basis of previous studies supporting its bipolar nature. METHODS: Consecutive 336 Bipolar II Disorder (BP-II), and 224 Major Depressive Disorder (MDD) outpatients were cross-sectionally assessed for major depressive episode (MDE) and concurrent DSM-IV hypomanic symptoms when presenting for treatment of depression, by a mood disorder specialist psychiatrist using the Structured Clinical Interview for DSM-IV as modified by Akiskal and Benazzi (J Clin Psychiatry, 2005) and the Hypomania Interview Guide (HIG), in a private practice. Mixed depression was defined as co-occurrence of MDE and hypomanic symptoms. Early age at onset (EO) below 21 years was used as diagnostic validator. RESULTS: Multivariable logistic regression of EO versus all within-MDE hypomanic symptoms, controlled for BP-II, showed that no specific symptom was independently associated with EO. By ROC analysis versus EO, the best combination of sensitivity and specificity, and the highest figure of correctly classified, were shown by a cutoff number >=3 symptoms, and by a cutoff HIG score >=8. Both cutoffs had similar strength of association with EO. Mixed depression defined by >=3 within-MDE hypomanic symptoms (A), or by a HIG score >=8 (B), were more frequent in EO group versus LO group (A: 70.5% versus 49.8%; B: 60.7% versus 40.9%; p<0.001), and in BP-II versus MDD (A: 72.3% versus 39.7%; p<0.001; positive predictive value for BP-II=73.1%; B: 63.9% versus 29.0%; p<0.001; positive predictive value for BP-II=76.7%). DISCUSSION: Findings could support the diagnostic validity of a definition of mixed depression based on a cutoff number/score of within-depression hypomanic symptoms versus one based on specific symptoms, complementing and supporting previous studies using bipolar family history as validator. Diagnosing mixed depression has treatment impacts, such as careful use of antidepressants added to mood stabilising agents or no use of antidepressants, as recently shown by large naturalistic and controlled studies.     

Anoxic-ischemic encephalopathy

Introduction: Prognostic determination of patients in coma after resuscitation from cardiac arrest is both common and difficult. We explored clinical and electrophysiological testing to determine their associations with favorable and poor outcomes. Methods: We studied 75 comatose patients resuscitated from cardiac arrest, excluding those who were brain dead or continuously sedated; none received hypothermia therapy. Clinical examinations were performed on day 1. Results: The following proportions recovered awareness: 2 of 18 patients with absent pupillary reflexes; 18 of 57 with preserved pupillary reflexes (p=0.08); 2 of 32 with absent corneal reflexes; 16 of 43 with preserved corneal reflexes (p=0.001); 0 of 15 with absent oculovestibular reflexes; and 8 of 29 with preserved oculovestibular reflexes (p<0.037). Purposeful movements were associated with a high probability of recovery, whereas other categories were unfavorable. Other categories of motor response were associated with an increased proportion of those who died without recovering awareness, but each category had some survivors. Somatosensory evoked potentials (SSEPs) were recorded from 47 patients. One of 21 patients with loss of the N20 component survived, compared with survival of 11 of 26 patients in whom it was present (p=0.003). All 5 patients with preserved N70 responses recovered awareness in a subgroup of 33 patients. Sixteen of 22 subjects with mild electroencephalogram (EEG) abnormalities recovered consciousness, compared with the survival of 3 of 50 patients with malignant EEG patterns (p= 0.0000001). Combining SSEP with EEG findings produced even greater predictive value. Conclusion: It seems unlikely that any single test will prove to have 100% predictive value for outcome; further studies combining clinical, EEG, and SSEP testing are warranted.     

Valproate-associated encephalopathy

Valproate (VPA) has been infrequently associated with encephalopathy. This was possibly the effect of secondary hyperammonemia or co-medications such as phenobarbital or phenytoin. We describe several patients with primary generalized seizures who had acute febrile delirium with alternating periods of stupor, confusion, and agitation shortly after initiating VPA therapy. They were without signs of hepatic dysfunction or medication toxicity, and they had no evidence of acute cerebral lesions. These observations suggest that VPA may produce delirium by direct central nervous system effects, possibly mediated by γ-aminobutyric acid pathways. Young adults with pre-existing encephalopathy may be at greater risk, especially those with generalized epilepsy.     

Hashimoto encephalopathy

Hashimoto encephalopathy is a chronic relapsing steroid responsive encephalopathy characterized by antibodies against thyroid components. Etiology is still unknown. Confusion, seizures and coma are frequent reported symptoms. We present a 65-year old patient with acute onset of partial seizures and cognitive impairment. Hashimoto encephalopathy was assumed with diagnosis of Hashimoto thyroiditis and clinical syndrome. Symptoms resolved with thyroid treatment alone. Hashimoto encephalopathy should be considered in patients with unexplained encephalopathy, even when thyroid function seems to be normal.