UMEM Educational Pearls - By Nicholas Contillo

Acute ischemic strokes involving the posterior circulation have significantly lower rates of hemorrhagic transformation after thrombolysis compared to anterior circulation strokes, a difference attributed to smaller infarct sizes and greater “ischemic tolerance” in the posterior circulation. 

Given this lower hemorrhage risk, the EXPECTS trial evaluated the safety and efficacy of extending the thrombolysis window to 4.5–24 hours in patients with acute posterior circulation ischemic stroke who were not candidates for endovascular thrombectomy. This randomized controlled trial, conducted across 30 sites in China, enrolled 234 adults with mainly mild posterior circulation stroke (median NIHSS 3) and no evidence of extensive infarction on CT. Participants were randomized to receive either intravenous alteplase or standard medical care within the 4.5–24 hour window after symptom onset. 

The primary outcome of functional independence at 90 days (modified Rankin Scale 0–2) was achieved in 89.6% of the alteplase group versus 72.6% of the standard care group. Rates of symptomatic intracranial hemorrhage were low and similar between groups (1.7% alteplase vs. 0.9% standard care), and 90-day mortality was lower in the alteplase group (5.2% vs. 8.5%). 

These findings support extending the therapeutic window for intravenous thrombolysis in posterior circulation stroke beyond 4.5 hours when thrombectomy is not an option. However, the trial’s limitations, including a study population predominantly with mild strokes, exclusion of patients with extensive infarction, and enrollment limited to Chinese centers, warrant further investigation in larger and more diverse populations. 

Bottom Line: Within limitations, emerging evidence supports an extended thrombolytic window beyond 4.5 hours for patients with posterior circulation strokes who are ineligible for thrombectomy.

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Anticoagulation is the mainstay of treatment of cerebral venous sinus thrombosis, irrespective of whether associated venous hemorrhage is present. Anticoagulant selection is variable, with physicians opting for unfractionated heparin (UFH) about 72% of the time in one international study. However, recent evidence favors the use of low-molecular-weight heparin (LMWH), with meta-analytic data showing trends towards lower mortality rates and improved functional outcomes in LMWH cohorts. UFH is often viewed more favorably due to the ability to rapidly discontinue the infusion in the event of major bleeding; however, risk of major bleeding complications were actually found to be lower in patients treated with LMWH compared to UFH. Further, LMWH has many pharmacological and practical benefits compared to UFH, including more predictable pharmacokinetics, reduced risk of heparin-induced thrombocytopenia (HIT), lack of need for frequent aPTT monitoring, ease of administration (daily subcutaneous injection), and ease of transition to outpatient therapy. 

Takeaway: Consider LMWH (1.5mg/kg subcutaneously once daily) as first-line treatment for CVST in patients with acceptable renal function.

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Multiple trials have aimed to assess the effect of blood pressure control in the prehospital setting for patients with suspected acute stroke.  The INTERACT-4 trial was a multicenter, prospective, randomized, open-label, blind endpoint trial conducted in China, in which 2404 hypertensive patients with suspected acute stroke (based on FAST score >2, symptom onset <2h, SBP >150mmHg) were randomized to receive urapidil versus usual care in the prehospital setting. The primary outcome was modified Rankin score (mRs) distribution at 90 days. Overall, no significant difference in functional outcomes at 90 days were observed in the urapidil versus usual care groups (OR 1.00, 95% CI 0.87-1.15). However, when analyzed by stroke type, improved functional outcomes and lower rates of rebleeding were seen in patients with hemorrhagic stroke (46.5% of all enrolled patients), while worsened functional outcomes and mortality were seen in patients with ischemic stroke. These observations are consistent with standard practices of intensive blood pressure reduction in patients found to have ICH, versus the “permissive hypertension” approach to patients found to have cerebrovascular occlusion. The results of this trial are not practice-changing, but do highlight the importance of prompt stroke recognition, streamlined hospital workflows for expedited diagnostics (CT), and timely initiation of antihypertensive therapy in ICH patients. 

Bottom line: Prehospital blood pressure reduction was not shown to improve clinical outcomes in hypertensive patients suspected to have acute undifferentiated stroke.

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Intrathecal baclofen pumps are increasingly used to manage spasticity in patients with conditions such as cerebral palsy, spinal cord injury, multiple sclerosis, traumatic brain injury, and other dystonias. The most common causes of baclofen pump dysfunction include pump-related issues (e.g., programming errors, battery failure), catheter problems (e.g., extra-thecal dislodgement, kinking, leaks), and medication depletion (e.g., overdue or insufficient refills). Symptoms of dysfunction can be nonspecific, ranging from mild (spasticity, dysphoria, dysesthesias) to severe (e.g., rigidity, rhabdomyolysis, seizures, fever, autonomic dysfunction, cardiomyopathy).

Once dysfunction is recognized, management involves stabilizing vital functions (ABCs, temperature management, fluids), administering multimodal antispasmodics (enteral or parenteral baclofen, benzodiazepines, dexmedetomidine, tizanidine), and performing pump interrogation, often in collaboration with neurology or PM&R specialists. Restoration of intrathecal flow is the preferred and definitive therapy; however, patients with severe withdrawal may require aggressive temporizing measures including intubation. Some authors describe intrathecal baclofen administration via lumbar puncture as a rescue measure for severe cases with limited access to definitive care. Imaging with plain radiographs, fluoroscopy, or CT may be indicated in select cases where there is concern for catheter displacement or kinking, and some patients may require surgical revision.

Takeaway: Consider baclofen withdrawal in patients on chronic baclofen therapy who present with nonspecific symptoms that may mimic conditions such as alcohol withdrawal, delirium, sympathomimetic toxicity, neuroleptic malignant syndrome, serotonin syndrome, thyrotoxicosis, rhabdomyolysis, sepsis, or status epilepticus. In cases of intrathecal pump dysfunction, the definitive treatment is restoration of baclofen flow, so involve consultants early for pump interrogation while temporizing with supportive measures.

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