Walking naturally after spinal cord injury using a brain-spine interface.

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis1,2. Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain-spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking4-6. A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

An Accurate and Rapidly Calibrating Speech Neuroprosthesis.

BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy. METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice. RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours. CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).

Quadriparesis and paraparesis following chimeric antigen receptor T-cell therapy in children and adolescents.

ABSTRACT: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART) therapy, characterized by the development of acute neurologic symptoms following CART infusion. ICANS encompasses a wide clinical spectrum typified by mild to severe encephalopathy, seizures, and/or cerebral edema. As more patients have been treated with CART, new ICANS phenomenology has emerged. We present the clinical course of 5 children who developed acute onset of quadriparesis or paraparesis associated with abnormal brain and/or spine neuroimaging after infusion of CD19- or CD22-directed CART, adverse events not previously reported in children. Orthogonal data from autopsy studies, cerebrospinal fluid (CSF) flow cytometry, and CSF proteomics/cytokine profiling demonstrated chronic white matter destruction, but a notable lack of inflammatory pathologic changes and cell populations. Instead, children with quadriparesis or paraparesis post-CART therapy had lower levels of proinflammatory cytokines, such as interferon gamma, CCL17, CCL23, and CXCL10, than those who did not develop quadriparesis or paraparesis. Taken together, these findings imply a noninflammatory source of this newly described ICANS phenomenon in children. The pathophysiology of some neurologic symptoms following CART may therefore have a more complex etiology than exclusive T-cell activation and excessive cytokine production.

Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria.

BACKGROUND: Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication. METHODS: We implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them. RESULTS: We decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period. CONCLUSIONS: In a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.).

Neurological and neuromuscular manifestations in patients with West Nile neuroinvasive disease, Belgrade area, Serbia, season 2022.

INTRODUCTION: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease. METHODS: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale. RESULTS: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively).

Neurological outcome following delayed traction and fixation in severe tetraparesis consecutive to posterior decompression for Chiari malformation: a case report.

BACKGROUND: Chiari malformation type 1 (CM1) is a congenital hindbrain malformation characterized by herniation of the cerebellar tonsils below the foramen magnum. The term Chiari type 1.5 is used when herniation of the brainstem under the McRae line and anomalies of the craniovertebral junction are also present. These conditions are associated with several symptoms and signs, including headache, neck pain, and spinal cord syndrome. For symptomatic patients, surgical decompression is recommended. When radiographic indicators of craniovertebral junction (CVJ) instability or symptoms related to ventral brainstem compression are present, CVJ fixation should also be considered. CASE DESCRIPTION: We report the case of a 13-year-old girl who presented with severe tetraparesis after posterior decompression for Chiari malformation type 1.5, followed 5 days later by partial C2 laminectomy. Several months after the initial surgery, she underwent two fixations, first without and then with intraoperative cervical traction, leading to significant neurological improvement. DISCUSSION AND CONCLUSION: This case report underscores the importance of meticulous radiological analysis before CM surgery. For CM 1.5 patients with basilar invagination, CVJ fixation is recommended, and C2 laminectomy should be avoided. In the event of significant clinical deterioration due to nonadherence to these guidelines, our findings highlight the importance of traction with increased extension before fixation, even years after initial destabilizing surgery.

The effect of level of injury on diabetes incidence and mortality after spinal cord injury - a longitudinal cohort study.

STUDY DESIGN: Retrospective longitudinal cohort study of veterans with SCI. OBJECTIVES: Spinal cord injury (SCI) is associated with an increased risk of developing diabetes mellitus (DM), likely due to body composition alterations and autonomic nervous system dysfunction. These factors are more pronounced in persons with tetraplegia (TP) versus paraplegia (PP). However, the effect of level of injury (LOI) on DM incidence is largely unknown. Therefore, the objective is to examine the effect of LOI on DM incidence in persons with SCI. SETTING: South Texas Veterans Health Care System. METHODS: We obtained electronic record data on age, sex, race/ethnicity, LOI and HbA1c concentration from January 1st 2001 through December 31st 2021. Cox proportional hazard regression analyses were used to assess the association between LOI, DM and all-cause mortality. RESULTS: Among 728 non-diabetic veterans with SCI (350 TP/ 378 PP, 52 ± 15 years, 690 male/38 female) 243 developed DM, of which 116 with TP and 127 with PP. Despite chronological variations between TP and PP, DM risk over the entire follow-up did not differ between the groups (hazard ratio (HR): 1.06, 95% CI: 0.82-1.38). Mortality was higher in TP versus PP (HR: 1.40, 95% CI: 1.09-1.78). However, developing DM did not increase the risk of death, regardless of LOI (HR: 1.07, 95% CI: 0.83-1.37). CONCLUSION: Despite chronological variations between both groups, the level of injury had minimal effect on long-term DM development in this cohort of veterans with SCI. Sponsorship NIH (DK105379; MS), RR&D SPiRE (I21RX003724-01A1; MT and SH).

High intensity functional training for people with spinal cord injury & their care partners.

STUDY DESIGN: Non-randomized clinical trial. OBJECTIVES: Examine the feasibility, physical and psychosocial effects of a high intensity functional training (HIFT) exercise program for people with spinal cord injury (pSCI) and their care partners (CPs). SETTING: Community fitness center in a Medically Underserved Area (Fort Smith, USA.) METHODS: A single-group design with three assessment points (before the program, at midpoint (13 weeks), and post-program (25 weeks) was used to examine the effects of up to 49 HIFT sessions over 25-weeks. Sessions were 60 to 75 min in duration and adapted to the abilities of participants. Feasibility measures included recruitment, retention, attendance, safety and fidelity (exercise intensity rated via session-Rating of Perceived Exertion (RPE). Physical measures included cardiovascular endurance, anaerobic power, and muscular strength. Psychosocial measures included perceived social support for exercise, exercise self-efficacy and health-related quality of life. RESULTS: Fourteen pSCI (7 with paraplegia and 7 with tetraplegia, 2 females) and 6 CPs (4 females) were included (median age = 60) (IQR = 15.8). Recruitment rates were 40% for pSCI and 32% for CPs. On average, participants attended 73% (22%) of exercise sessions with a median session-RPE of 5 (IQR = 1). Retention rates were 83% and 67% for pSCI and CPs, respectively. For pSCI and their CPs, large effect sizes were observed for cardiovascular endurance, anaerobic power, muscular strength, and social support for exercise. CONCLUSIONS: For pSCI and their CPs, HIFT appears feasible and potentially leads to improvements in physical and psychosocial health for both groups.

A case of iatrogenic acute spinal cord injury with tetraplegia following thyroid surgery.

AIM: Iatrogenic acute spinal cord injury with tetraplegia is a serious consequence of non-spinal surgery.We report a case of acute spinal cord injury with tetraplegia after thyroid surgery. METHOD: The patient was pathologically diagnosed with papillary carcinoma, underwent left thyroidectomy, and developed tetraplegia after surgery. RESULT: The patient was diagnosed with acute spinal cord injury with tetraplegia and cured after anti-inflammatory and dehydrating treatment. CONCLUSION: Iatrogenic spinal cord injuries after elective non-spinal surgery can have catastrophic consequences, and clinicians must be alert to this possibility in clinical practice.

Thyrotoxic Periodic Paralysis: A Rare Cause of Quadriparesis in a Young and Seemingly Healthy Patient.

Hypokalemia is a common laboratory finding in hospitalized patients, typically resulting from insufficient potassium intake, renal or gastrointestinal losses, or intracellular shifts. While the underlying cause is often easily identifiable, certain cases present diagnostic challenges, and if left unrecognized, the consequences can be life-threatening. We report a rare and atypical case of severe symptomatic hypokalemia as the initial presentation of newly diagnosed Graves' disease. The condition was caused by thyrotoxic periodic paralysis, a rare but serious complication of thyrotoxicosis, predominantly seen in East Asian populations. This disorder is characterized by episodes of acute, reversible muscle weakness associated with transient hypokalemia, which increases the risk of falls and traumatic injuries. The prompt identification of the etiology in such cases is critical for preventing recurrence and avoiding potentially fatal complications.

Learned Motor Patterns Are Replayed in Human Motor Cortex during Sleep.

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain-computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep.SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain-computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain-computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.

A neuropsychiatric case of delayed post-hypoxic leukoencephalopathy from opioid intoxication resulting in Anton-Babinski syndrome and quadriplegia.

This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation's pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments.

How did intraoperative neuromonitorization prevent tetraplegia?

PURPOSE: Patients with mucopolysaccharidosis type IVA (MPS IVA) have many risk factors for myelopathy and paresis. These are spinal cord compression, bone stenosis, and soft tissue thickening with ligament laxity, deformity, odontoid hypoplasia, and atlantoaxial instability. Although most patients with MPS IVA appear generally healthy at birth, patients often show skeletal deformities within a few years. Surgical indications are difficult to determine. Historically, many physicians have used prophylactic decompression and fusion in young, asymptomatic MPS IVA patients to prevent cord compression. Although spinal cord decompression is usually required at the craniocervical junction in patients with MPS IVA, decompression may be required at other spinal cord levels as well. There is a risk of developing neurological damage during surgery. The most common causes are ischemia secondary to cardiac output deteriorated in the prone position or due to artery damage, and local trauma due to neck movements or traction while bringing the patient to the prone position. Neurophysiological monitoring is very important during surgery to reduce the risk of neurological damage in spinal cord surgery. In this case report, a case with loss of lower extremity neuromonitorization motor evoked potential (MEP) responses in the early period of surgery without any intervention to the craniocervical junction after prone positioning will be presented.

The feasibility of using mouthpiece ventilation in the intensive care unit for post-extubation breathing support after acute tetraplegia.

STUDY DESIGN: A prospective cohort of patients with acute tetraplegia. OBJECTIVES: This study aimed to determine the feasibility of using mouthpiece ventilation (MPV) in the intensive care unit (ICU) for patients who are extubated after suffering an acute cervical spinal cord injury (CSCI). SETTING: ICU, Princess Alexandra Hospital, Brisbane Australia. METHODS: New admissions to ICU in the 14 months between April 2017 and June 2018 with a CSCI who underwent intubation were assessed for inclusion. MPV was provided to consenting participants (who were deemed likely to be able to maintain ventilation on their own) at the time of extubation and was utilised in addition to standard care while participants were awake. MPV settings, usage, and support hours to educate and facilitate MPV were collected. Feedback from participants and clinical staff was gathered throughout the study. Pre- and post-extubation measures of forced vital capacity (FVC), the frequency of endotracheal suction of sputum, and gas exchange using ventilation-perfusion ratios were recorded along with the incidence of reintubation. RESULTS: Fourteen participated in utilising MPV with 16 episodes of extubation. The average time per participant to have MPV titrated and bedside data collected was 178 minutes. Data from 16 episodes of extubation have been included. Three of the 14 participants failed initial extubation. Feedback from participants and clinicians has been positive and constructive, enabling MPV settings to be adapted to the person with acute CSCI during this pilot study. CONCLUSION: MPV is feasible to use post-extubation for people with CSCI in ICU. Pressure control mode MPV was deemed the most suitable for newly extubated acute CSCI patients. Intensive clinical support is required initially to provide education prior to MPV, and at the time of extubation for both patient and treating clinicians. Both report it to be a useful adjunct to ICU treatment.

Grasp and Release Test for Tetraplegic Hand Assessment: an update of the Grasp and Release Test.

The Grasp and Release Test (GRT) was originally developed to measure effectiveness of an implanted neuroprosthesis in people with tetraplegia. Its ease of use and lack of floor and ceiling effects culminated in recommendations for inclusion in a battery of tests to measure outcome following upper limb reconstructive surgery. However, the length of time taken to administer the GRT in a clinical setting, lack of instructions of accepted grasp patterns in the upper limb reconstructive surgery population and scoring procedures lead to differences in reporting outcomes using this measure. In order to ensure clinical utility for the upper limb reconstructive surgery population, revisions of the original test instructions have been made and are reported in this article. Further testing of the psychometric properties of the new measure are currently underway.

Test-retest reliability of short- and long-term heart rate variability in individuals with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate test-retest reliability of heart rate variability (HRV) metrics in SCI without restriction of activity over long (24-h) and shorter durations (5-min, 10-min, 1-h, 3-h and 6-h). SETTINGS: University hospital in Khon Kaen, Thailand. METHODS: Forty-five participants (11 with tetraplegia and 34 with paraplegia) underwent two 24-h recordings of RR-intervals to derive time and frequency HRV metrics. Relative reliability was assessed by intraclass correlation coefficient (ICC) and absolute reliability by coefficient of variation (CV) and Bland-Altman limits of agreement (LoA). RESULTS: For 5- and 10-min durations, eight of eleven HRV metrics had moderate to excellent reliability (ICC 0.40-0.76); the remaining three were poor (ICC < 0.4). HRV values from 1-h and 3-h durations showed moderate to excellent reliability (ICC of 0.46-0.81), except for 1-h reliability of ULF and TP (ICC of 0.06 and 0.30, respectively). Relative reliability was excellent (ICC of 0.77-0.92) for 6-h and 24-h durations in all HRV metrics. Absolute reliability improved as recording duration increased (lower CVs and narrower LoAs). Participants with high AD risk (SCI level at or above T6) showed lower test-retest reliability of HF and LF values than participants with low AD risk. CONCLUSION: Relative reliability of HRV was excellent for 6-h and 24-h. The best absolute reliability values were for 24-h duration. Time-domain outcomes were more reliable than frequency domain outcomes. Participants with high risk of AD, particularly those with tetraplegia, showed lower reliability, especially for HF and LF.

Quantifying Tenodesis Hand Function in Cervical Spinal Cord Injury: Implications for Function.

PURPOSE: Cervical spinal cord injury (SCI) has a profound effect on upper-extremity function. Individuals with stiffness and/or spasticity may have more, or less, useful tenodesis function. This study examined the variability present before any reconstructive surgery. METHODS: Tenodesis pinch and grasp were measured with the wrist in maximal active extension. Tenodesis pinch was the contact point of the thumb with the index finger proximal phalanx (T-IF:P1), middle phalanx (T-IF:P2), distal phalanx (T-IF:P3), or absent (T-IF:absent). Tenodesis grasp was the distance from the long finger to the distal palmar crease (LF-DPC). Activities of daily living function was assessed using the Spinal Cord Independence Measure (SCIM). RESULTS: The study included 27 individuals (4 females, 23 males; mean age 36 years, mean time since SCI 6.8 years). The mean International Classification for Surgery of the Hand in Tetraplegia (ICSHT) group classification was 3. In the dominant hand, individuals with a T-IF tenodesis pinch to P1 or P2 had significantly higher total SCIM scores (43.7 and 34.2, respectively) compared to those with absent T-IF tenodesis pinch (SCIM 17.8). Shorter LF-DPC distance with tenodesis grasp (improved finger closing) also correlated with improved SCIM mobility and total scores. No association was found between the ICSHT group and SCIM score or tenodesis measures. CONCLUSIONS: Quantifying tenodesis with pinch (T-IF) and grasp (LF-DPC) is a simple method to characterize hand movement in individuals with cervical SCI. Better tenodesis pinch and grasp were associated with improved activities of daily living performance. CLINICAL RELEVANCE: Differences in grasp function have implications for mobility, and differences in pinch function have implications for all functions, particularly self-care. These physical measurements could be used to assess movement changes after nonsurgical and surgical treatment in tetraplegia.

Subacute ascending myelopathy in adolescent athlete after spinal cord injury: a case report on dynamic complication of spine trauma.

BACKGROUND: Subacute post-traumatic ascending myelopathy (SPAM) is a rare complication after spinal cord injury (SCI). SPAM onsets within few days or weeks after initial SCI. Here, we present an adolescent male athlete who developed SPAM after SCI and brief review of literature. Previous reports almost all were about adult patients. Here, we present second adolescent case in the literature. CASE DESCRIPTION: A 15 years old adolescent athlete presented to A&E with a T10-T11 fracture dislocation of the spine and a SCI. He underwent T9-L1 posterior instrumentation and decompression. On the 11th post injury, he complained numbness of the T4 dermatome and by the 14th day, he had become tetraplegia with paralysis of the arms and required ventilation. MRI revealed C3-T10 cord changes on T2 weighed images. He received high dose methylprednisolone for 3 weeks. At one-year follow up he had fully recovered arm motor power and improved light touch and pin prick sensation. CONCLUSIONS: SPAM may occur in adolescents with a good prognosis. Our case is well example against for proposal of arterial hypothesis.

Acute Porphyria: An Unusual Case Of Quadriparesis, Hypertension, Recurrent Severe Cyclic Abdominal Pain, And Seizures.

Porphyria refers to a rare group of genetically inherited or acquired disorders that arise due to reduced metabolic activity of any of the enzymes in the haem biosynthetic pathway. Defect in any enzyme causes the presentation of symptoms of porphyria. The epidemiology of Acute Intermittent Porphyria (AIP) is complicated because of its rarity and delay in diagnosis. We present the case of a seven-year-old girl who presented with multisystem involvement; her symptoms were quadriparesis, hypertension, recurrent severe cyclic abdominal pain, and seizures. These symptoms together were not explained by the differentials taken into account. She presented before puberty with no family history of such conditions, while being born of consanguineous marriage. Her symptoms along with urinary porphobilinogen positivity test helped to reach the diagnosis of AIP in the absence of cutaneous manifestations. This case highlights the variable presentation of porphyria and emphasises the importance of appropriate and timely diagnosis and management in these patients.

Restoring cortical control of functional movement in a human with quadriplegia.

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.