Acute transitory head mislocalization - a novel syndrome of pathological embodiment in a patient with traumatic brain injury - a case study.

Feeling of body ownership is a complex process with different brain mechanisms involved in integrating the varied and multiple representations of the body . The ability to discriminate between one's own and others' body parts can be lost after brain damage. We report a unique case study of a patient with head injury who experienced a phenomenon where he felt that his head was positioned with another person standing next to him. We describe this as a form of pathological embodiment and call it the "head mislocalization" phenomenon. We report his clinical findings and using the methods of lesion mapping and lesion network mapping postulate the neural mechanisms for this symptom.

Sensitivity and specificity of phrenic nerve electrophysiology to predict mechanical ventilation in the Guillain-Barré syndrome.

INTRODUCTION/AIMS: In Guillain-Barré syndrome (GBS), the sensitivity and specificity of phrenic compound muscle action potential (CMAP) measurements to predict endotracheal mechanical ventilation are unknown. Hence, we sought to estimate sensitivity and specificity. METHODS: We performed a 10-year retrospective analysis of adult GBS patients from our single-center laboratory database (2009 to 2019). The phrenic nerve amplitudes and latencies before ventilation were recorded along with other clinical and demographic features. Receiver operating curve (ROC) analysis with area under the curve (AUC) was used to determine the sensitivity and specificity with 95% confidence interval (CI) for phrenic amplitudes and latencies in predicting the need for mechanical ventilation. RESULTS: Two hundred five phrenic nerves were analyzed in 105 patients. The mean age was 46.1 ± 16.2 years, with 60% of them being male. Fourteen patients (13.3%) required mechanical ventilation. The average phrenic amplitudes were lower in the ventilated group (P = .003), but average latencies did not differ (P = .133). ROC analysis confirmed that phrenic amplitudes could predict respiratory failure (AUC = 0.76; 95% CI, 0.61 to 0.91; P < .002), but phrenic latencies could not (AUC = 0.60; 95% CI, 0.46 to 0.73; P = .256). The best threshold for amplitude was ≥0.6 mV, with sensitivity, specificity, and positive and negative predictive values of 85.7%, 58.2%, 24.0%, and 96.4%, respectively. DISCUSSION: Our study suggests that phrenic CMAP amplitudes can predict the need for mechanical ventilation in GBS. In contrast, phrenic CMAP latencies are not reliable. The high negative predictive value of phrenic CMAP amplitudes ≥0.6 mV can preclude mechanical ventilation, making these a useful adjunct to clinical decision-making.

Transcranial Doppler Screening for Patent Foramen Ovale Closure in Cryptogenic Strokes in Young: A Single Center Experience from South India.

BACKGROUND: Cryptogenic strokes are common in young adults. Patent foramen ovale (PFO) is an important cause of cryptogenic ischemic strokes. Transcranial Doppler (TCD) with bubble contrast is a noninvasive bedside tool in screening for PFO and other right to left shunt (R-L shunt). Percutaneous PFO closure in selected patients with a high risk for paradoxical emboli is beneficial. Data on PFO in young cryptogenic strokes from India are limited. AIMS: To determine the utility of screening for R-L shunt using TCD in young patients with cryptogenic strokes and to identify clinical predictors of an R-L shunt. MATERIALS AND METHODS: This was a hospital-based prospective study conducted between January 2013 and December 2019 in a tertiary hospital in South India. All consecutive patients with ischemic stroke and ages between 18 and 45 years were included. TCD with bubble contrast study was performed on all patients. Those who were TCD bubble contrast study positive and had features of an embolic stroke of undetermined source (ESUS) underwent transesophageal echocardiography (TEE) to confirm a PFO and to look for its high-risk features. Selected ESUS patients with PFO and associated high-risk features as identified on TEE underwent percutaneous PFO device closure. All patients were followed up in the stroke and cardiology clinics. RESULTS: During the study period, 6,197 patients with ischemic strokes were screened for eligibility of which 304 (4.9%) were between the age of 18 and 45 years. Of these, 300 patients with ischemic stroke in young underwent the TCD bubble contrast study. R-L shunt was found in 121 (40.3%) patients. Based on an extensive etiological evaluation, 72 patients were identified to have an ESUS and underwent TEE for confirming PFO. Of these, 65 patients had PFO, four were negative, and three were found to have extracardiac shunts. Based on clinical findings, imaging features, and high-risk features on TEE, 29 patients underwent PFO closure. Activity at the time of stroke onset equivalent to a Valsalva maneuver (p ≤ 0.01), isolated cortical infarction (p = 0.027), and posterior circulation involvement (p = 0.0135) were significantly associated with the presence of an R-L shunt. The patients who had a higher modified anatomical-functional risk of paradoxical embolism (AF-RoPE) score, a high-grade shunt on the TCD bubble contrast study had a longer length of the tunnel and had the presence of an interatrial septal aneurysm (p = 0.012) were referred for PFO device closure. CONCLUSIONS: R-L shunt is common in cryptogenic ischemic strokes in young. TCD with bubble contrast study is a noninvasive and feasible bedside tool to detect them. Applying the ESUS criteria in these cryptogenic strokes with a positive TCD bubble contrast study can be then used for selecting patients for more invasive tests like TEE. High-risk PFOs picked up with TEE can be then considered for PFO closure for secondary stroke prevention. The history of Valsalva maneuver-like activity (such as lifting heavy weights or straining) at the time of stroke onset can be a clinical predictor for the presence of an R-L shunt. In addition to isolated cortical infarction, the presence of posterior circulation infarct in ESUS can predict the presence of an R-L shunt.

Monoclonal Gammopathies of 'Neurological Significance': Paraproteinemic Neuropathies.

OBJECTIVES: To study the clinical profile and outcomes of patients with paraproteinemic neuropathy (PPN) and to explore the utility of nerve conduction studies (NCSs) to differentiate between the demyelinating subtypes. METHODS: We did a retrospective analysis of patients diagnosed with PPN between January 2010 and December 2019 in an inpatient setting. The study population consisted of patients above 16 years of age presenting with clinical features suggestive of chronic peripheral neuropathy and on evaluation was found to have PPN. RESULTS: A total of 74 patients were identified. The patients were predominantly in the 6th decade, and the majority were males. The subtypes of PPN were monoclonal gammopathy of undetermined significance (MGUS) (45.9%), POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) (24.3%), solitary plasmacytoma (17.6%), multiple myeloma (8.1%), and AL amyloidosis (4.1%). There are specific features on NCS which can help in identifying POEMS syndrome and IgM MGUS. The majority of patients with PPN tend to stabilize or improve with treatment; however, many have a severe residual disability. New terminology and classification of these entities as 'monoclonal gammopathies of neurological significance' can aid in early diagnosis and the development of effective treatment, to prevent residual disability. CONCLUSION: PPN has a heterogeneous spectrum of clinical, biochemical, and electrophysiological features. NCS can help distinguish POEMS syndrome and IgM MGUS from other demyelinating subtypes.

Chronic flaccid quadriparesis from tract specific myelopathy in neurosyphilis.

INTRODUCTION: Tract-specific myelopathies with distinctive imaging features are uncommon and typically occur with metabolic or paraneoplastic syndromes. We report a unique case of tract-specific myelopathy with neurosyphilis. CASE PRESENTATION: A 53-year-old male presented with a four-month history of flaccid quadriparesis, sensory loss, and bladder dysfunction. His MRIs revealed striking symmetric T2-weighted hyperintensities in the lateral corticospinal tracts and dorsal columns of the cervical spinal cord that extended rostrally into the pyramidal decussation and medial lemnisci of the medulla oblongata. Nerve conduction and needle electromyography studies excluded axonal or demyelinating lower motor neuron disorders. The patient reported previous untreated primary syphilis and was seropositive on the T.pallidum hemagglutination assay. Penicillin therapy resulted in substantial clinical improvement. DISCUSSION: Although syphilitic meningomyelitis is well-reported, our patient was unique because of the persistent flaccidity (possibly suggesting prolonged spinal shock) and striking tract-specific MRI patterns. These features are novel in syphilitic myelitis and suggest unknown mechanisms of tract-specific tropism and neuronal injury. CONCLUSIONS: "Tract-specific" complete transverse myelopathy with persistent flaccid weakness and areflexia is a novel presentation of neurosyphilis. Early recognition and crystalline penicillin therapy can alleviate morbidity. Our report describes this patient's findings and discusses the differential diagnoses of tract-specific myelopathies.

Cerebral venous sinus thrombosis: changing trends in the incidence, age and gender (findings from the CMC Vellore CVT registry).

BACKGROUND: Multiple cerebral venous sinus thrombosis (CVT) registries from various geographical regions indicate that female gender, the use of contraceptive pills, pregnancy and puerperium are important risk factors. In this study, we report the changes in the epidemiology of patients with CVT managed over the past 26 years. METHODS: The CMC Vellore CVT registry is a prospectively maintained database at the Christian Medical College, Vellore since January 1995. Stata software was used to analyse the data and assess the changes in the incidence, age and gender distribution over the previous 26 years. RESULTS: Among 1701 patients treated during the study period, 908 (53%) were women and 793 (47%) were men. The mean incidence of CVT was 49 per 100 000 admissions before 2010, which increased to 96 per 100 000 after 2010. Male gender had a higher odds of developing CVT (OR - 2.07 (CI 1.68 to 2.55, p<0.001). This could be attributed to the declining incidence of postpartum CVT after 2010 compared with the decade before 2010 (50% vs 20%). The mean age at presentation had increased from 24.5 to 33.2 years in the last decade. CONCLUSIONS: There was a clear change in the gender pattern from being a condition with female preponderance, to one where equal or more men are being affected. Lower incidence of postpartum CVT cases could be the driving factor. An increase in the overall incidence of CVT cases was noted, probably due to a higher index of clinical suspicion and better diagnostic imaging modalities.

Opsoclonus myoclonus ataxia syndrome, ovarian teratoma and anti-NMDAR antibody: an 'unresolved' mystery.

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the combination of opsoclonus and arrhythmic action myoclonus with axial ataxia and dysarthria. In adults, a majority are paraneoplastic secondary to solid organ tumours and could harbour antibodies against intracellular epitopes; however, certain proportions have detectable antibodies to various neuronal cell surface antigens. Anti-N-methyl-D-aspartate (NMDAR) antibodies and ovarian teratomas have been implicated in OMAS. Methods: Report of two cases and review of literature. Results: Two middle-aged women presented with subacute-onset, rapidly progressive OMAS and behavioural changes consistent with psychosis. The first patient had detectable antibodies to NMDAR in the cerebrospinal fluid (CSF) alone. Evaluation for ovarian teratoma was negative. The second patient had no detectable antibodies in serum or CSF; however, she had an underlying ovarian teratoma. Patient A was treated with pulse steroids, therapeutic plasma exchange (TPE) followed by bortezomib (BOR) and dexamethasone, while patient B was treated with steroids, TPE followed by surgical resection of ovarian teratoma. Both patients had favourable outcomes and were asymptomatic at the 6 monthly follow-up. Conclusions: With coexistent neuropsychiatric manifestations, OMAS can be considered a distinct entity of autoimmune encephalitis, pathogenesis being immune activation against known/unknown neuronal cell surface antigens. The observation of absence of anti-NMDAR antibody in patients with teratoma-associated OMAS and vice versa is intriguing. Further research on the potential role of ovarian teratoma in evoking neuronal autoimmunity and its targets is required. The management challenge in both cases including the potential use of BOR has been highlighted.

Dissociative pseudo-ulnar sensory loss in a patient with a focal haemorrhage secondary to cerebral venous thrombosis - A case report.

INTRODUCTION: Small cortical strokes can mimic weakness of peripheral nerve lesions. However, isolated sensory deficits involving the fingers due to cortical lesions are rare. METHODS: We present a case of a 46 year old man with cerebral venous thrombosis, and a haemorrhage restricted to the postcentral gyrus, who reported numbness in an ulnar neuropathy-like distribution. Testing of somatosensory (SSEP) and pain-related evoked potential (PREP) was done, and the lesion location was mapped to the template brain. RESULTS: The patient had impaired touch and pain but preserved proprioception. He had a normal SSEP response but a prolonged PREP. The lesion was mapped to Broadmann areas 1 and 3b of the postcentral gyrus. DISCUSSION: Sensory cortical representation is such that, the ulnar fingers are medial, and the radial ones are lateral. Also, modality-specific organization is noted with tactile sensation being mapped to areas 1 and 3b, and proprioceptive sensation to area 3a and 2. Thus focal lesions involving the post central gyrus can have selective sensory loss over some fingers and can have selective impairment of some modalities. CONCLUSIONS: We highlight the rare finding of an ulnar-like sensory loss in a patient with cerebral venous thrombosis and the dissociate nature of the sensory loss in isolated cortical lesions.

Neural Correlates of Hiccups in Patients with Lateral Medullary Infarction.

Background: Hiccups is a known presentation of lateral medullary infarction. However, the region in the medulla associated with this finding is not clearly known. In this study, we aimed to study the neural correlates of hiccups in patients with lateral medullary infarction (LMI). Methods: This retrospective study included all patients who presented with lateral medullary infarction between January 2008 and May 2018. Patients with hiccups following LMI were identified as cases and those with no hiccups but who had LMI were taken as controls. The magnetic resonance imaging of the brain was done viewed and individual lesions were mapped manually to the template brain. Voxel-based lesion-symptom mapping employing nonparametric permutation testing was performed using MRIcron. Results: There were a total of 31 patients with LMI who presented to the hospital during the study period. There were 11 (35.5%) patients with hiccups. Using the voxel-based lesion-symptom mapping analysis, the dorso-lateral region of the middle medulla showed significant association with hiccups. Conclusion: In patients with LMI, we postulate that damage to the dorsolateral aspect on the middle medulla could result in hiccups.

Epstein-Barr virus infection in a woman with aquaporin-4 seropositive neuromyelitis optica.

Neuromyelitis optica spectrum disorders (NMOSD) are characterised by pathological antibodies to aquaporin-4 water channels of astrocytes, resulting in severe brain and spinal cord injury. Serological evidence suggests that Epstein-Barr virus (EBV) reactivation may contribute to their pathogenesis. We describe an unusual case of a woman with fever, rash and headache preceding an Aquaporin-4 antibody positive longitudinally extensive transverse myelitis. EBV was detected in her cerebrospinal fluid by polymerase chain reaction assay. This case highlights the potential role of EBV in the pathogenesis of NMOSD.

Utility of Serial Nerve Conduction Studies in the Electrodiagnosis of Guillain-Barre Syndrome.

BACKGROUND: Guillain-Barre syndrome can be electrophysiologically classified into demyelinating and axonal subtypes and nerve conduction studies remain the mainstay in electrodiagnosis. Accurate electrodiagnosis has both therapeutic and prognostic significance and different criteria sets have been proposed for classification. OBJECTIVES: To electrophysiologically classify GBS patients into AIDP and axonal subtypes according to various published criteria (Cornblath, 1990: Hadden, 1998, Rajabally, 2015), investigate if serial NCS changes the classification, and to identify additional parameters which may support the electrodiagnosis. MATERIALS AND METHODS: In a retrospective study, we included all patients aged 15 to 80 years, admitted with a diagnosis of GBS between August 2015 and July 2017, who had at least two serial NCS. The various published criteria were applied to the two serial NCS and subtype classification along with diagnostic shifts on serial NCS were ascertained. RESULTS: At the first test, the established criteria gave a yield of 45.2% to 71% for AIDP, while 29% to 54.8% of patients were classified as axonal GBS. In the second study, there was a change in electrodiagnosis, ranging from 9.6% to 16.1%. The resolution of reversible conduction failure and misclassification of subtypes were the major reason for diagnostic shifts. Sural sparing pattern, facial nerve dysfunction, abnormal blink reflex, and phrenic nerve dysfunction were more common in AIDP. CONCLUSIONS: Serial nerve conduction studies allow an accurate electrodiagnosis of GBS subtypes, which has both therapeutic and prognostic implications. Also, the use of additional parameters such as blink reflex facial and phrenic nerve conduction may supplement routine NCS.

Role of Pain-Related Evoked Potential in the Diagnosis of Meralgia Paresthetica.

INTRODUCTION: Entrapment of the lateral femoral cutaneous nerve (LFCN) of thigh results in meralgia paresthetica (MP). Standard electrophysiological tests for MP are technically demanding and unreliable. We aimed to study the role of pain-related evoked potentials (PREP) in the diagnosis of MP. METHODS: Patients with MP and normal volunteers were included. PREP was recorded by stimulating the skin over the lateral thigh 20 cm below the anterior-superior iliac spine and recording from the cortex at Cz. RESULTS: A total of 28 subjects and 56 LFCNs were studied. 36 nerves had MP and 20 were normal. The mean PREP latency was 118 (8) ms among normal controls and 164 (10.8) ms in MP. The optimal cut-off point for the diagnosis of MP was 134 ms. Area under receiver operator characteristic curve was 0.97; sensitivity was 91.7% and specificity was 100%. CONCLUSION: PREP is reliable and easy to use electrophysiological test in establishing the diagnosis of MP.

Postural Sway and Bobblehead Movement: Unique Presentation of Bilateral Tendo-Achilles Rupture.

The human body requires equilibrium to assume the vertical posture and balance for walking which is maintained by righting reflexes and supporting reactions, respectively. Postural movements around the ankle is responsible for maintaining forward and backward leaning in an upright posture. We report a case of postural sway and bobblehead movement following bilateral tendo-Achilles rupture.

Network Localization of Central Hypoventilation Syndrome in Lateral Medullary Infarction.

BACKGROUND AND PURPOSE: The brainstem plays a key role in the control of respiration. Strokes involving the lateral medulla can rarely produce a central hypoventilation syndrome (CHS) characterized by loss of automatic respiration called Ondine's curse. In this study, we investigated the neuroanatomical correlates of CHS in patients with lateral medullary infarction (LMI). METHODS: Cases of CHS following LMI were identified from searching our medical records and literature. Voxel-based lesion-symptom mapping and lesion network-symptom-mapping (LNSM) analysis was performed to identify the regions connected to the lesion sites based on normative functional connectome data. RESULTS: Sixteen patients with CHS and 32 controls were included. The ventro-lateral region of the rostral medulla showed a significant association with CHS. LNSM analysis showed connections of this region to the rostral ventro-lateral medulla and caudal pons. CONCLUSIONS: In patients with LMI, disruption of the respiratory control network, at the level of ventro-lateral region of the rostral medulla, could result in CHS.

Peduncular hallucinosis in 'top of the basilar syndrome': an unusual complication following coronary angiography.

Cerebral thromboembolism is a potential, although rare, complication of coronary angiography. An elderly woman presented with visual hallucinations, features of bilateral third nerve palsy, impaired vertical and horizontal gaze and mild motor weakness of the left upper limb, following diagnostic coronary catheterization. These findings suggested the anatomical location of the lesion to lie in the caudal midbrain, which was confirmed on computed tomography of the brain. Peduncular hallucinosis following cardiac catheterization, to the best of our knowledge, has only been described once in the literature. Awareness of this entity and its clinical presentation is essential for appropriate investigation and management.

Clinical profile of primary progressive aphasias in a tertiary care centre from India.

Purpose: Progressive language dysfunction due to a selective neurodegeneration of the language networks is called primary progressive aphasia (PPA). However, demographic data on PPA is limited. In this study from India, we determined the prevalence and clinical profile of patients presenting with PPA and its subtypes.Method: Patients who were admitted to the neurosciences department during the period between January 2012 and December 2016 were screened, and patients who presented with slowly progressive aphasia for at least 2 years without other significant cognitive or behavioural symptoms and preservation of daily living activities were included. Patients had to fulfil the international consensus group criteria for PPA. All patients were evaluated with the mini-mental status examination (MMSE) and Strub and Black battery for neuropsychological testing. The language was tested using the progressive aphasia language scale (PALS).Result: During the study period from January 2012 to December 2016, 23 patients fulfilled the international consensus criteria for PPA. Of these, 16 (69.6%) patients were diagnosed with PPA-G, 6 (26%) patients had PPA-S and 1 (4.4%) patient had PPA-L.Conclusion: PPA is not an uncommon entity in India and the most common subtype in this study was PPA-G.

Neural Correlates of Urinary Retention in Lateral Medullary Infarction.

PURPOSE: The brainstem plays an important role in the control of micturition, and brainstem strokes are known to present with micturition dysfunction. Micturition dysfunction in cases of lateral medullary infarction (LMI) is uncommon, but often manifests as urinary retention. In this study, we investigated the neuro-anatomical correlates of urinary retention in patients with LMI. METHODS: This was a hospital-based retrospective study conducted in the neurology unit of a quaternary-level teaching hospital. Inpatient records from January 2008 to May 2018 were searched using a computerized database. Cases of isolated LMI were identified and those with micturition dysfunction were reviewed. MRI brain images of all patients were viewed, and individual lesions were mapped onto the Montreal Neurological Institute (MNI) space manually using MRIcron. Nonparametric mapping toolbox software was used for voxel-based lesion-symptom analysis. The Liebermeister test was used for statistical analysis, and the resultant statistical map was displayed on the MNI template using MRIcron. RESULTS: During the study period, 31 patients with isolated LMI were identified. Their mean age was 48 years and 28 (90%) were male. Six of these patients (19%) developed micturition dysfunction. All 6 patients had urinary retention and 1 patient each had urge incontinence and overflow incontinence. In patients with LMI, the lateral tegmentum of the medulla showed a significant association with urinary retention. CONCLUSION: In patients with isolated LMI, we postulate that disruption of the descending pathway from the pontine micturition centre to the sacral spinal cord at the level of the lateral tegmentum results in urinary retention.

Timed Vibration Sense and Joint Position Sense Testing in the Diagnosis of Distal Sensory Polyneuropathy.

INTRODUCTION: Distal sensory polyneuropathy (DSP) is one of the most common neurological disorders. Although several studies have studied the role of the neurological examination in DSP, there are only limited studies on the utility of timed vibration sense (VBS) and joint position sense (JPS) testing in the diagnosis of DSP. OBJECTIVES: The objective is to study the utility of timed VBS testing and JPS testing at the great toe in clinical detection of DSP. METHODS: This study was prospectively conducted in the neurology department of a tertiary care hospital in India. Patients with DSP referred to the electrophysiology laboratory from August 2017 to December 2017 were screened. Patients with symptomatic DSP which was confirmed by electrophysiological studies were taken as cases and normal participants with no symptoms or electrophysiological findings suggestive of DSP served as controls. RESULTS: We studied 127 patients and 194 controls. The mean age of the patients was 48.7 (14.5) years in the patient group and 39.7 (14.5) years in the control group. The male: female ratio was 77/50 in the patient group and 112/82 in the control group. Abnormal clinical examination was found in 95% of the patients with DSP. The most common abnormal examination components were impaired ankle reflexes (70%), vibration (85%), and JPS (39.6%) sensation. Using the receiver operating characteristic curve for the diagnosis of DSP, a vibratory response lasting <8 s at the great toe had a sensitivity of 85% and specificity of 42.8%. For JPS testing at the great toe, obtaining two or more incorrect responses had a sensitivity of 33% and specificity of 87.6%. CONCLUSION: VBS testing was more sensitive and JPS testing was more specific in making a clinical diagnosis of DSP. For timed VBS, duration of >8 s at the great toe was a useful test to rule out DSP, and for JPS testing at the great toe, obtaining two or more incorrect responses was a useful test in ruling in the diagnosis of DSP.

Delayed-onset encephalopathy and coma in acute organophosphate poisoning in humans.

The objective of the study was to describe the clinical characteristics and course of delayed-onset organophosphate (OP) poisoning. In our clinical experience, we have noticed patients with onset of deep coma 4-7 days after hospital admission, clinical features that have not been previously described. We set up a prospective observational study over 1 year to formally characterize this observation. Thirty-five patients admitted to the intensive care unit (ICU) with severe OP poisoning and treated with atropine and supportive therapy were followed up. Oximes were not administered. Three patients developed delayed-onset coma after presenting with normal or near normal Glasgow coma score (GCS). They developed altered conscious state rapidly progressing to deep coma, 5.0+/-1.0 (mean+/-S.D.) days after OP ingestion. The GCS persisted at 2T for 4.3+/-2.1 days despite the cessation of sedative drugs at the onset of coma. During this period, the patients had miosed non-reacting pupils and no clinically detectable cortical or brainstem activity. Computed tomography of the brain and cerebrospinal fluid analysis were normal. Electroencephalogram showed bihemispheric slow wave disturbances. Two patients required atropine during this period to maintain heart rate and reduce secretions. In all three patients, no metabolic, infective or non-infective cause of altered conscious state was identified. With supportive therapy the GCS improved to 10T in 8.0+/-2.0 days. All patients survived to hospital discharge. Three other patients who developed a reduction in GCS (3T-7T) by 4.7+/-1.2 days but not progressing to coma and recovering (GCS 10T) in 3.3+/-0.6 days may have manifested delayed-onset encephalopathy. Delayed-onset coma appears to have a distinct clinical profile and course with complete resolution of symptoms with supportive therapy. Although persistent cholinesterase inhibition is likely to have contributed to the manifestations, the mechanism of coma and encephalopathy need to be explored in further trials. The good outcomes in these patients suggest that therapy should not be limited in OP-poisoned patients developing profound coma or encephalopathy during hospitalization.