UMEM Educational Pearls - Neurology

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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• Antimicrobial medications can be associated with neurological adverse reactions. 
• An individual’s risk is influenced by their age, weight, nutritional status, the medications they are taking concurrently, and pharmacological properties (dosage, half-life, CNS permeability). 
• Encephalopathy 
  • Seen with beta-lactams, fluoroquinolones, clarithromycin, and sulfamethoxazole-trimethoprim. 
  • Most commonly with cefepime. 
  • Higher risk in elderly, renal dysfunction, and preexisting CNS disease. 
• Seizures 
  • Beta-lactams block GABA receptors. 
  • Highest risk with cefepime and imipenem. 
• Peripheral neuropathy 
  • Associated with metronidazole, fluoroquinolones, linezolid, chloramphenicol, and isoniazid. 
  • Most cases are dose dependent. 
  • Some cases are irreversible. 
• Ototoxicity 
  • Aminoglycosides cause cochlear NMDA receptor excitotoxicity. 
• Weakness 
  • Fluoroquinolones, macrolides, and aminoglycosides inhibit acetylcholine release and bind neuromuscular junction receptors. 
  • Should be avoided in myasthenia gravis and Lambert-Eaton syndrome. 
• Movement disorders 
  • Tremors – sulfamethoxazole-trimethoprim 
  • Dyskinesia, dystonic reactions – fluoroquinolones, chloramphenicol 
  • Cerebellar syndrome – metronidazole, aminoglycosides 

Bottom Line: Recognition of antibiotic associated neurotoxicity reduces unnecessary workup and serious adverse effects. 

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Ventriculoperitoneal (VP) shunts are common. Unfortunately shunt complications are also common! 

There are 3 major categories of shunt complications:

1. Mechanical Failure - obstruction, fracture, disconnection, migration, perforation
2. Functional Failure - overdrainage, slit ventricle syndrome, pseudocyst, ascites, meastasis
3. Infection - may occur in  up to 10% of patients (bacterial, fungal, parasitic)

Shunt series are helpful, but are NOT 100% sensitive. If you have a clinical concern for a shunt complication, make sure to involve neurosurgery.

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Your patient presents with a large traumatic subdural hematoma with midline shift and clinical evidence of herniation.  Your nearest neurosurgeon is several hours away, what do you do?

Initial resuscitation should follow ATLS.  Treatment of intracranial hypertension and herniation includes elevating the head of bed, administering osmotic therapies, optimizing analgesia/sedation, and hyperventilation.  If all measures have been exhausted and there is a delay to definitive neurosurgical intervention, an emergency department burr hole may be considered.

Indications:

• GCS < 8, dilated and nonreactive pupil(s), posturing suggestive of uncal or transtentorial herniation 
• Radiographic evidence of an extra-axial (subdural/epidural) hematoma causing midline shift and brainstem compression
• Lack of timely neurosurgical intervention
• Procedure will not delay transfer to definitive care

Contraindications:

• Neurosurgical intervention available within reasonable time frame
• Skull fracture at site of planned burr hole

Equipment:

• Razor
• Surgical marker
• Sterile prep and drape
• Syringe, needle, lidocaine
• Scalpel, forceps, retractor, sharp hook, scissors
• Hand drill, hex wrench, drill bit with guard
• Sterile saline, gauze, dressing

Transtemporal Approach:

• Measure skull thickness on CT for depth of drill guard.
• Position patient supine and elevate the ipsilateral shoulder with a shoulder roll.  Utilize tape or have assistant hold the head in place. 
• Shave the hair.
• Mark the point 2 cm superior and 2 cm anterior to the tragus.
• Sterile prep and drape.
• Inject local anesthetic and then make a 3 cm vertical skin incision down to the periosteum.  Dissect and use a retractor to expose the skull.
• Drill with steady pressure perpendicular to the skull.  Irrigate with sterile saline to remove bone fragments.
• Once the skull is penetrated:
  • If an epidural hematoma, blood should be released.  Can use sterile saline to facilitate drainage of clotted blood.
  • If a subdural hematoma, use a sharp hook to tent the dura and make a small cruciate incision.
• Place loose sterile dressing.
• Transfer to definitive care.

Additional Points:

• Neurosurgery consultation before performing this procedure is recommended. 
• Antibiotic prophylaxis with gram-positive coverage is recommended.
• In extenuating circumstances, this may be considered without CT confirmation of the location of the extra-axial hematoma.  However, there is risk of a negative exploratory burr hole due to a hematoma not in the temporal location or due to a false localizing sign.

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Study Question:  A recent study investigated whether a history of concussion caused greater disturbances in cerebral blood flow and cerebral white matter after subsequent concussions.

Background:  Researchers used changes in blood flow in the cingulate cortex and white matter microstructure in the corpus callosum as evidence of underlying brain injury.

Population:  228 athletes with an average age of 20.  Divided into 2 groups, recent and non-recent concussion.

61 athletes had a recent (uncomplicated) concussion and 167 did not. Within the first group, 36 had a history of concussion. Within the second group, 73 had a history of concussion.

Note: researchers used “self-reported” history of concussion in study.

Intervention: Researchers took up to 5 MRI scans of each recently concussed athlete. This encompassed the acute phase of injury (1 to 7 days post-injury), the subacute phase (8 to 14 days), medical clearance to return to sport, one month post return and one year post return.

The sport concussion assessment tool (SCAT) was also used to evaluate effects of history of concussion on symptoms, cognition and balance.

Results:  One year after a recent concussion, those athletes with a history of concussion had sharper declines in blood flow within one area of the cingulate cortex compared to those without a history of prior concussions.

Athletes with a history of concussion had an average cerebral blood flow of 40 mL per minute, per 100 grams of brain tissue.

Athletes without a history of concussion had an average cerebral blood flow of 53 mL per minute, per 100g of brain tissue.

In the weeks following concussion, those athletes with a prior history of concussion had microstructural changes in the corpus callosum.

 Effects were seen in the absence of differences in SCAT domains or time to return to sport.

Conclusion:  Athletes with a history of concussion experience identifiable injury to their brains as evidenced by changes in blow flow and white matter microstructure.  Athletes “cleared” for return to play following concussion may be at greater risk of subtle patterns of brain injury versus their peers.

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• The landscape of acute ischemic stroke treatment changed dramatically with endovascular thrombectomy (EVT).
• However, few patients with basilar artery occlusions were included in major EVT trials.
• Basilar artery occlusion accounts for 10% of large vessel occlusions and can result in devastating neurological deficits.
• The recently published BASICS trial evaluated the efficacy of EVT within 6 hours of symptom onset in 300 patients with basilar artery occlusion strokes.
• 44.2% of the EVT group had a good outcome compared to 37.7% of the medical treatment group (p=0.19).
  • Good outcome was defined as modified Rankin scale of 0 (no symptoms) to 3 (moderate disability but able to walk without assistance) at 90 days.
  • Symptomatic intracranial hemorrhage was higher in the EVT group (4.5% vs. 0.7%, p=0.06).
  • History of AFib was more common in the EVT group (28.6% vs. 15.1%).
• It is important to note that this study did not use advanced neuroimaging for patient selection unlike in landmark EVT trials of anterior circulation large vessel occlusion strokes.

Bottom Line: There is no significant difference between endovascular thrombectomy and medical management for basilar artery occlusion strokes within 6 hours of symptom onset. 

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• Post-lumbar puncture (LP) headache, reported in up to 33% of patients, is due to a persistent CSF leak causing intracranial hypotension.
• A recent review by Cognat et al. looked to answer several frequently asked clinical questions:
  • Who is at decreased risk of post-LP headache?
    • Infants and children have a similar prevalence compared to adults.
    • Older patients have a lower risk, with an incidence of <5% in those over 60 years old.
  • Does needle choice minimize the risk of post-LP headache?
    • Atraumatic non-cutting ("Whiteacre" or "Sprotte") needles have lower rates (RR 0.4, 0.34-0.47).
    • The use of atraumatic needles does not affect the rate of success, success on first attempt, or duration of the LP.
  • Does performing the LP in a specific way prevent post-LP headache?
    • LPs performed in the lateral decubitus position and at a higher intervertebral space have a lower incidence.
    • Difficult LPs (e.g. multiple attempts, traumatic tap) do not appear to affect the rate.
    • The volume of CSF removed does not affect the rate.
  • Do any treatments after the LP reduce post-LP headache occurrence?
    • Bed rest after LP does not reduce and may in fact worsen the likelihood.
    • Fluids and caffeine do not prevent post-LP headaches.

Bottom Line: The use of atraumatic needles is most effective in reducing the risk of post-LP headaches. These needles are easy to use and have similar rate of success as cutting needles.

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• Functional neurological disorders (FND) are unintentional and involuntary. 
• Imaging and electrophysiological studies have shown cerebral dysfunctions in attention and perception, which may explain why symptoms often improve with distraction. 
• Diagnosis requires demonstration of inconsistency and/or incongruency with recognized neurological or medical conditions. 
  • No clinical sign alone is diagnostic. 
  • Patients may have comorbidities such as multiple sclerosis, stroke, or epilepsy. 
• Hoover’s sign and drift without pronation have been described as positive signs for FND. 
  • These can also be seen in patients with pain, neglect, or apraxia. 
• Avoid maneuvers that may harm the patient, such as dropping their arm onto their face. 
  • A high-pitched tuning fork applied to the nostrils is an effective stimulus to assess responsiveness.  
• Avoid using terms like non-organic, psychogenic, or pseudoseizure. 
• When counseling a patient, avoid only explaining what conditions they do not have or attributing symptoms to psychological problems or stress. 
  • Instead, name the diagnosis, explain that their symptoms are real and common, and emphasize that symptoms are potentially reversible. 
• Early diagnosis of FND is associated with improved physical and psychological outcomes. 

Bottom Line: Functional neurological disorders (FND) are commonly encountered in the ED. A thorough neurological exam may reveal positive signs suggestive of FND. Early diagnosis and referral to specialists may improve outcomes. 

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• Alteplase administration in acute ischemic stroke (AIS) has been associated with errors.
• A recent study looked at the types of errors that occurred at regional hospitals and Comprehensive Stroke Centers.
• 19.8% (133/676) of patients had an error associated with alteplase administration with the majority occurring at regional hospitals without stroke certification.
  • The most common error was over-dosage of alteplase, occurring in 5% (36) of patients.
  • Other common errors included under-dosage, infusion errors, and apparent contraindications.
• The most common contributing factor leading to the error was incorrect calculation.
• Administration error was associated with higher rate of hemorrhagic conversion (12.7% vs. 7.1%, p=0.04).

Bottom Line: Alteplase administration in acute ischemic stroke is associated with errors, most commonly with over-dosage of the medication.

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• Idiopathic intracranial hypertension (IIH) predominantly affects women of childbearing age and is strongly associated with obesity.
• Patients can have high rates of healthcare utilization due to their chronic disabling headaches, multiple diagnostic tests and specialist consultations, and potential complications related to treatments.
• A recent study looked at trends in the incidence, prevalence, and healthcare outcomes of IIH in the 3.1 million Welsh population over a 14-year period.
  • Incidence of IIH increased from 2.3/100,000 to 7.8/100,000 (p<0.001).
  • Prevalence of IIH increased from 12/100,000 to 76/100,000 (p<0.001).
  • Obesity (BMI >30 kg/m2) also increased from 29% to 40% of the population (p<0.001), with IIH incidence and prevalence strongly associated with BMI.
  • Outcomes included blindness (0.78%), moderate visual impairment (1.9%), CSF diversion (9%) with 44% of these patients requiring at least 1 revision surgery.
  • IIH patients also had 5.28 times higher rate of unscheduled hospital visits during this time period.

Bottom Line: The incidence and prevalence of IIH is increasing, likely related to rising rate of obesity. This has also been associated with more healthcare utilization compared to the general population.

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• Bell’s palsy can be caused by herpes simplex virus-1 (HIV-1) and Lyme borreliosis.
• Prior studies have found higher incidence of Bell’s palsy in colder months possibly related to reactivation of latent HSV-1.
• A recent study looked at the incidence and seasonal variation of positive Lyme tests in Bell’s palsy patients in a Lyme-endemic area (New Jersey).
  • Over a 5-year period, 81% of 442 patients with Bell’s palsy were tested for Lyme and 16% tested positive.
  • The months May through October had a 7.2 times higher incidence of positive Lyme tests in Bell’s palsy patients, with the peak in July.
  • May through October also had a 1.3-fold increased ED visits for Bell’s palsy, also peaking in July.

Bottom Line: In a Lyme-endemic area, the incidence of positive Lyme tests and Bell’s palsy are highest in the Lyme months. This seasonal variation may help guide the management of patients with Bell’s palsy.

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• Most seizures resolve spontaneously, however, seizures that persist >5 minutes or recur without the patient returning to their baseline should be treated expeditiously with benzodiazepines and antiepileptic medications.
• A subset of patients may continue to have electrographic seizures despite cessation of their convulsive seizure activity.
  • Prior studies described 26-52% of patients develop nonconvulsive seizures after resolution of convulsive status epilepticus.
• The recent Established Status Epilepticus Treatment Trial (ESETT) compared fosphenytoin, levetiracetam, and valproic acid in aborting seizures and improving responsiveness in patients who did not response to initial treatment with benzodiazepines.
  • EEG was not required for this trial, but 58% (278/478) had an EEG within 24 hours after seizure onset.
    • Of those who had an EEG, 14% (39/278) had electrographic seizures.
  • For patients who had clinical treatment success, 13% (13/102) were found to have electrographic seizures.

Bottom Line: Persistent or recurrent seizures are not uncommon in the first 24 hours after status epilepticus even in patients with resolved clinical seizure activity. Early use of EEG can help identify patients who need further escalation of treatment.

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• Acute ischemic stroke patients are commonly admitted to an ICU after receiving IV tPA to be closely monitored for potential complications.
• Current post-tPA protocol requires frequent vital signs and neurological assessments up to every 15 minutes, thereby requiring 1:1 or 1:2 nurse-to-patient ratio.
• Studies have shown that stroke severity is a strong predictor of the need for critical care interventions for post-tPA patients, where patients with an NIHSS score ≥10 have an ~8x higher odds of requiring critical care interventions than those with NIHSS <10.
• A low-intensity post-tPA monitoring protocol (Figure 1) for patients with NIHSS <10 and no critical care needs has been found to be safe in a small single center study.
  • These low risk patients were admitted with telemetry monitoring and 1:3 nurse-to-patient ratio after an initial period of q15 min standard monitoring.
  • An international, multicenter, randomized controlled trial is being planned to study this further.

• This strategy may help streamline care and utilize hospital resources more efficiently in the COVID-19 pandemic and beyond.

Bottom Line: Patients with NIHSS <10 may be safe for low-intensity post-tPA monitoring if they do not require critical care after an initial period of q15 min standard monitoring for the first 2 hours.

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• Prior studies have shown that ethnic minorities have lower levels of stroke knowledge and lower penetrance of public health stroke education.
• A recent study looked at whether patients’ language preference affects acute ischemic stroke care metrics.
  • 3190 stroke patients at an urban Comprehensive Stroke Center, where 300 (9.4%) had a non-English preferred language
  • They found no difference in:
    • Time from symptom discovery to ED arrival (128 min vs. 161 min for patients with English preferred language, p=0.68)
    • Arrival by EMS (65% vs. 61.3%, p=0.21)
    • Door-to-imaging time (55 min vs. 60 min, p=0.33)
    • Door-to-needle time for thrombolysis (51 min vs. 53 min, p=0.69)

Bottom Line: Patients' language preference does not appear to affect the efficiency of acute ischemic stroke care, especially at experienced high volume stroke centers. 

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• Migraine is the 2nd most common neurologic disorder after tension headache and accounts for more disability than all other neurologic disorders combined.
• Diagnosis is clinical and defined by at least 5 episodes of headache that meet the following criteria:
  • Duration of 4 to 72 hours (when untreated or unsuccessfully treated)
  • At least 2 characteristics: unilateral, pulsating, moderate-to-severe pain intensity, aggravated by physical activity
  • Accompanied by at least 1 symptom: nausea, vomiting, photophobia, phonophobia
• Aura symptoms must be fully reversible and may be visual, sensory, speech/language, motor, brainstem, or retinal.
• Early treatment while the headache is still mild include NSAIDs followed by triptans.
  • Opioids and barbiturates are not recommended due to adverse effects and risk of dependency.
• Preventive treatment is recommended for patients who have at least 2 migraine days per month and whose lives are adversely affected.
  • Common therapies include antihypertensive agents (e.g. propranolol), antidepressants (e.g. amitriptyline), anticonvulsants (e.g. topiramate, valproate), and calcium-channel blockers (flunarizine).

Bottom Line: Migraine is a common and debilitating condition that benefits from early treatment. Consider initiating preventive therapy for patients who experience at least 2 migraine days per month and adverse effects despite treatment.

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• When dealing with weakness and sensory complaints in the ED, the time course of symptoms and physical exam findings help identify emergent conditions.
• We often talk about upper motor neuron vs. lower motor neuron signs that distinguish whether a lesion is in the central or peripheral nervous system.
• Characteristics that differentiate between central vs. peripheral nervous system pathology include:

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• We've talked about the rising incidence of cerebral venous thrombosis (CVT) and choice of neuroimaging studies before, now let’s talk about presentation and treatment.
• Symptoms range from headache to coma with cerebral edema and intracranial hypertension depending on the veins and sinuses involved.
  • Superior sagittal sinus is most frequently affected (62%) and can cause headache, hemiparesis, hemisensory loss, hemianopia, and seizures.
  • Transverse sinus is also commonly involved (45%) and can cause headache, aphasia, and seizures.
  • Thrombosis of the deep veins is seen in 18% of cases and can cause altered mental status, coma, and gaze palsy.
• Management includes anticoagulation, treatment of underlying cause, seizures, and intracranial hypertension.
  • LMWH is preferred unless in patients with renal dysfunction or need for rapid reversal of anticoagulation.
  • Endovascular intervention may be considered in severe cases that do not improve or deteriorate despite anticoagulation.
• Poor prognostic factors are: 
  • 2 points each - malignancy, coma, deep venous thrombosis
  • 1 point each - mental status disturbances, male, intracranial hemorrhage
  • Score ≥3 suggests high risk of poor outcome

Bottom Line: Severity of CVT presentation depends on the location and clot burden. Anticoagulation is key, though consider endovascular intervention if patient does not improve or deteriorates despite anticoagulation.

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