Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

The elbow flex-ex: a new sign to detect unilateral upper extremity non-organic paresis.

OBJECTIVE: To examine a new neurological sign that uses synergistic oppositional movements of the arms to evaluate for non-organic upper extremity weakness. METHODS: Patients with unilateral arm weakness were tested in a standing or sitting position with the elbows flexed at 30°. The examiner held both forearms near the wrists while asking the patient to flex or extend the normal arm at the elbow and simultaneously feeling for flexion or extension of the contralateral (paretic) arm. In patients with organic paresis, there was not a significant detectable force of contralateral opposition of the paretic limb. Patients with non-organic arm weakness had detectable strength of contralateral opposition in the paretic arm when the normal arm was tested. RESULTS: The test was first performed on 23 patients with no complaint of arm weakness. Then, 31 patients with unilateral arm weakness were tested (10 with non-organic weakness and 21 with organic weakness). The elbow flex-ex sign correctly identified the cause of weakness in all cases. CONCLUSIONS: The elbow flex-ex sign is useful in differentiating between functional and organic arm paresis.

Symptom spread to contiguous body parts as a presentation of cerebral ischemia.

BACKGROUND: Ischemic stroke commonly presents with sudden onset of focal deficit that is maximal at onset. Symptom onset marked by the spread of symptoms to contiguous body parts may suggest migraine, seizure or cerebral amyloid angiopathy (CAA) that is mimicking ischemic symptoms. OBJECTIVE: To assess (1) if the spread of symptoms to contiguous body parts is an uncommon presentation of ischemic stroke and transient ischemic attack (TIA) and (2) if patients presenting with this symptom complex frequently have migraine, seizure or CAA mimicking stroke or TIA. METHODS: 110 consecutive patients presenting with stroke-like symptoms were prospectively evaluated for symptoms at onset, abnormalities on cerebral imaging, risk factors for stroke, discharge diagnosis, and development of subsequent TIA/stroke, migraine, seizure, or cerebral hemorrhage during follow-up. RESULTS: Of patients able to give a history of symptoms at onset, 23% described symptoms spreading to contiguous body parts. None had a history of migraine or seizure. None had clinical course or imaging features typical of CAA. During follow-up, 1 was diagnosed with migrainous stroke and none had suffered seizure or intracranial hemorrhage. CONCLUSIONS: The spread of symptoms to contiguous body parts is not uncommon at the onset of ischemic TIA/stroke. In our series, migrainous stroke was much less common and none had evidence of seizure or CAA.