Transient worsening of residual neurological deficit or recurrence of previous neurological
deficit has been observed in patients with previous stroke. Recurrent stroke or transient
ischemic attack (TIA) are frequent causes with a cumulative recurrence rate around
5.4% at 1 year.[1] Other causes may include Todd's paralysis, metabolic causes like hyponatremia, hypotension
or infections, and use of sedative drugs.[2]
[3] Herein, we report a case of transient reemergence of old stroke deficit with review
of literature.
A 42-year-old hypertensive male was admitted with complaints of altered sensorium
and acute onset left-sided weakness since last evening. He had history of right middle
cerebral artery (MCA) infarct 1 year back when he had left hemiparesis associated
with speech abnormality and facial deviation. He was managed conservatively and had
functional recovery to modified Rankin score (mRS) 1. On examination, he appeared
drowsy, irritable, dehydrated and had left side limbs power of medical research council
(MRC) grade 2. His vitals showed heart rate 99 per minute, blood pressure 137/87 mm
Hg, respiratory rate 18 per minute, and temperature 97.1°F. He was suspected to have
recurrent stroke. Diffusion-weighted magnetic resonance imaging (MRI) of brain showed
no diffusion restriction and, T2 weighted and FLAIR sequences showed hyperintense
area in right frontoparietal region suggestive of old infarct with gliosis along with
chronic infarct in right corona radiata. Electroencephalograph showed no epileptiform
discharges. Blood investigations revealed blood sugar level 106 mg/dL and hyponatremia
with serum sodium 122 mEq/L. Patient was admitted to intensive care unit with a provisional
diagnosis of metabolic encephalopathy with hypovolemic hyponatremia in view of signs
of dehydration, low serum osmolarity, and urine sodium levels. Hypertonic saline infusion
(3% sodium chloride) was started to treat hyponatremia along with supportive treatment.
Next day, his serum sodium level reached 137 mEq/L and he became alert with no irritability.
His left-sided limbs power improved to MRC grade 4. Later, he was shifted to ward
and discharged home.
Different authors have described reemergence phenomenon as post-stroke recrudescence
(PSR), recrudescence of old stroke deficits (ROSDs), or differential awakening.[2]
[4]
[5] This phenomenon was initially described by Cucchiara as “differential awakening”
when he observed that patients with cerebral ischemia or mass lesions developed neurological
deficits after awakening from anesthesia, which improved and returned to normal over
10 to 30 minutes.[4] Thal et al,[5] investigated the pharmacological effect of fentanyl and midazolam in patients with
brain tumors or carotid disease. Transient unmasking or reemergence of previous deficit
was observed in 73% patients with previously resolved or persisting deficit. Later,
Lazar et al,[3] investigated the role of midazolam in reemergence of stroke deficit in eight patients
with previous stroke. All patients demonstrated transient reemergence or worsening
of previous deficit, returning back to normal after 2 hours. Among the commonly used
anesthetic agents in current era, midazolam and propofol are most frequently associated
with sedation-induced transient neurological deficit.[6] Patients in propofol and midazolam group had median NIHSS (National institute of
health stroke scale) change of 2 to 3 points. The majority of score change was in
limb motor function. They also found that tumor type and grade also affected the sensitivity
to drugs. Post sedation NIHSS change was similar between gliomas and meningiomas,
with similar sensitivity to all four drugs in patients with high-grade gliomas. Role
of anatomical and functional changes in synaptic connectivity and receptor density
secondary to brain remodeling may be implicated. GABAA agonists have shown to reduce brain plasticity mediated by long-term potentiation
compared with anti-cholinergics.[7] This explains the drug specificity in causation of post-sedation neurological deficits.
Recently, various other triggers for reemergence of deficit have been identified in
patients with previous stroke, which include infection, dyselectrolytemia, and hypotension.[2]
[8] Exact mechanism of re-emergence phenomeon is not known, but role of neurotransmitters
like GABA (BZD, propofol), altered neuronal excitability or conduction (dyselectrolytemia),
or cytokine-mediated pathway (infection) have been implicated. Reemergence is more
frequently associated with small vessel infarcts, diabetes, dyslipidemia, and smoking.
It is predominantly seen after stroke affecting white matter, however, change in NIHSS
is similar in ischemic or hemorrhagic index stroke.[2] Incidence of reemergence is more when MCA territory (>70%) is involved during index
stroke.[2] The resolution of deficit usually occurs within 24 to 48 hours with correction or
reversal of the trigger.
Hyponatremia is frequent in patients with ischemic stroke with incidence up to 40%
and SIADH being most common cause. Risk factors for hyponatremia include poor solute
intake, site of infarction (MCA territory is most common), drugs like mannitol or
diuretics, secondary infections and inappropriate use of hypotonic fluids. Hyponatremia
can present as stroke mimic due to symptoms like altered sensorium, seizures, focal
neurological deficits, and coma. During acute change in sodium concentration aquaporin
four channels fail to upregulate in astrocytes. This prevents shunting of water into
astrocytes thereby increasing cellular volume and cerebral edema resulting in generalized
cerebral dysfunction. But mechanism of focal neurological deficits due to hyponatremia
is not well understood and is believed to be secondary to alteration in neuronal conduction
and excitability. Due to underreporting of reemergence phenomenon, exact frequency
of hyponatremia in PSR episodes cannot be estimated, but Topcuoglu et al[2] reported high frequency (18.5%) of hyponatremia in these episodes.
Reemergence phenomenon can be seen in emergency setting, postoperative period, or
after sedation for brain imaging. It should be promptly distinguished from mimics
like acute stroke, TIA, or Todd's paralysis as it may have management-related implications.
Therapy like intravenous thrombolysis (IVT) has associated risks and repeated imaging
increases radiation exposure, length of stay, and cost. Although IVT should not be
withheld in eligible patients suspected to have acute stroke. Other clinical implication
includes involving metabolic or infectious evaluation in suspected patients. Additionally,
sedative agents should be selected based on patient factors, features of previous
stroke, tumor type and grade. Neurological deficits are commonly limited to limbs
motor weakness but delirium or confusion is frequent. Diagnostic criteria may include:
(1) transient duration with spontaneous recovery after resolution of triggering factor,
(2) MRI suggestive of old stroke with no acute ischemia, (3) no clinical or electroencephalographic
evidence of seizure. Our patient developed irritability and reemergence of weakness
which resolved after correction of hyponatremia. His clinical features fit the diagnostic
criteria suggested by Topcuoglu et al.[2] To conclude, reemergence phenomenon is under-recognized due to poor knowledge or
understanding. It is crucial to promptly diagnose and differentiate it from mimics
to reduce error and improve outcome.
