Acute motor mutism and encephalopathy in older men Clinical reasoning

How should patients with acute motor mutism be targeted for a qualitative diagnosis? Is a history of sickle cell disease instructive in the diagnosis? The latest issue of the Neurology Journal Clinical Reasoning Series reports a case of acute motor mutilation and encephalopathy in 70-year-old men with a history of hemoglobin sickle cell disease, rheumatoid arthritis and non-idiopathic pulmonary embolism
.

Translation: Reflection without a trace

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Part I

The patient is a 70-year-old male, right-handed, African-American male who presents
with "severe abdominal and diffuse systemic pain for 5 days.
" There is a history of hemoglobin sickle cell disease (Hb SC), rheumatoid arthritis (RA), and non-idiopathic pulmonary embolism (PE) in the year prior to
presentation.
The patient did not take anticoagulants or any psychotropic drugs, but recently completed short-term steroid therapy (for joint pain
).
Initial evaluations including complete blood count (CBC), comprehensive metabolic set (CMP), lipase, urine culture, blood culture, urerotoxicology, and ambulatory and pelvic CT scans and enhancement scans were not significantly abnormal, except for leukocytosis (22,000
/^mm3) that is considered steroid-induced.
Subsequently, the patient received intravenous fluids and opioids for vascular occlusive pain crisis
.
On the 3rd day of hospitalization, the patient cannot speak, obey orders, or move his limbs
.

Physical examination showed normal vital signs, awake, spontaneous eye opening, intermittent tracking, pupil symmetry, isocircle, photosensitivity, normal head-eye reflex, and no asymmetry of
the face.
Negative signs of meningeal irritation; not making a sound, not being able to follow orders, very little spontaneous movement of the limbs, no response to stinging; Hyperreflexia of the extremities, normal muscle tone, and involuntary movements
.
Neuroimaging including head and neck CTA and MRI pan (including GRE sequences) did not reveal acute intracranial lesions
.
One week later, a follow-up MRI of the brain and SWI show multiple microbleeding on the screen (Figure 1
).
Cerebrospinal fluid (CSF) shows 0 white blood cells (WBC), 1 red blood cell (RBC), elevated protein 178 mg/dL and yellow stain.

EEG shows no epileptiform discharge
.

Figure 1 MRI examination
of the patient's skull.
(A) The SWI sequence shows multiple low-signal lesions in the subcortical region in a "Walnut Kernel" pattern
.
(B) DWI sequences show multiple high-signal patchy lesions of white matter in both deep and subcortic, "Starfield" mode
.

Problem Thinking:

1.
Positioning qualitative diagnosis?

Part II

Lack of spontaneous movement and speech, impaired comprehension is characteristic
of motor mutism.
The disease is a relatively rare neurological syndrome manifested by intact conscious and sensorimotor abilities, but reduced goal-oriented behaviors and decreased
mood.
The patient is in a very apathetic awake state, indifferent
to pain, thirst, or hunger.
Motor mutism must be distinguished from
coma (metabolic abnormalities or herniation syndrome), brainstem lesions such as encephalitis or osmotic demyelination, drug overdose (opioids, benzodiazepines, etc.
), basilar artery occlusion (atresia syndrome), and catatonia.

Motor mutism is difficult to localize and may result from damage to many areas of the brain, including the dorsal or prefrontal cortex, the subfrontal cortex, the anterior cingulate cortex, the caudal nucleus, the shell nucleus, the midbrain, or the thalamus
.

Differential diagnoses of motor mutism include ischemic or hemorrhagic infarction, septic cerebral embolism, primary or secondary vasculitis, bacterial or viral encephalitis, demyelinating disorders such as multiple sclerosis or acute disseminated encephalomyelitis, autoimmune encephalitis, sarcoidosis, other inflammatory encephalitis, primary central nervous system (CNS) malignancies (e.
g.
, lymphoma), and pipa meningeal cancer
.

Several subfrontal cortical structures, including the anterior cingulate cortex, the basal ganglia, the medial thalamus and ventral covered, and the dense part of the substantia nigra, are involved in the neural circuits
of motivation and motor initiation.
In this patient, diffuse microbleeding may disrupt the integration of information between the subcortical structures of the frontal lobe, leading to motor mutism
.

Problem Thinking:

1.
What are the differential diagnoses of hemorrhagic stroke involving multiple vascular distribution areas?

2.
What checks should I perform?

Part III

Differential diagnoses of hemorrhagic stroke involving multiple vascular distribution areas include trauma, cerebral amyloid vascular disease, reversible cerebrovasoconstrictive syndrome, metastatic tumors, central nervous system abscesses, or systemic infections such as endocarditis, vasculitis, and coagulation disorders
。 Cranial MRI shows abnormal T2 FLAIR high signal with linear and nodular enhancement, extensive SWI low signal involving radial crown, corpus callosum, periventricular white matter, basal ganglia, brainstem, and cerebellum, and microbleeding in accordance with the "Walnut Kernel" pattern; Bilateral deep and subcortical white matter diffusion is limited in accordance with the "Starfield" pattern (Figure 1), which suggests cerebral fat embolism (CFE
).

A follow-up CSF study showed elevated 2 WBC/μL, 5 RBC/μL, protein (129 mg/dL), and yellow staining (860 RBC/μL
).
Yellow stains may result from extensive microvascular injury, high CSF proteins, and disruption
of the blood-brain barrier.
There are no abnormalities in the CSR Research Laboratory and the meningitis set, flow cytometry and cytology tests
.
Repeated laboratories showed a decrease in hemoglobin from 10 to 8 gm/dL, platelets 50,000/mm3, reticulocyte count of 11%, lactate dehydrogenase 688 U/L, ferritin 780 ng/mL and haptoglobin <30 mg/dL, alkaline phosphatase 170 IU/L, and normal ADAMTS13 activity (111%)
.
Peripheral blood smear shows morphological abnormalities in red blood cells with teardrop-like cells, sickle cells, large platelets, and a large number of nucleated red blood cells, suggesting bone marrow necrosis
.

Antinuclear antibody spectra and rheumatoid factor positive with a titer of 1:160, consistent
with its RA diagnosis.
C-reactive protein and erythrocyte sedimentation rate are normal and do not support worsening of RA or other autoimmune diseases
.
Parvovirus B19 IgM, Lyme disease antibodies, and hepatitis intact were not abnormal
.

There are no abnormalities
in blood, urine, and cerebrospinal fluid cultures.
Chest , abdominal and pelvic CT scan and enhancement did not reveal significant infectious or neoplastic lesions
.
A full-body CT scan shows partial osteonecrosis
of the humerus head.
Transthoracic echocardiography reveals no vegetations or valvular lesions, and the bubble examination is normal to exclude sepsis or venous embolism
.
Brain DSA did not detect any significant macrovascular or mesovasculitis
.
Right frontal brain biopsy pathology shows parenchymal hemorrhagic foci and tissue necrosis with vacuolar formation, without evidence
of inflammation or vasculitis.

The patient is diagnosed with dyskinesiac mutism
secondary to CFE.
Fat embolism may be due to bone marrow necrosis due to underlying Hb SC disease
.

Diagnostic tests when CFE is suspected should include MRI of the skull with DWI and SWI sequences
.
Most reports of CFE in the literature occur in the case of a fracture of a long bone, but in the absence of trauma, the examination should include an assessment of the cause of
bone marrow necrosis.
Diagnostic tests should evaluate for hemoglobinopathy, coagulation/thrombotic disorders (eg, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, antiphospholipid syndrome), autoimmune disorders, infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome (AIDS), and malignancy
.

Problem Thinking:

1.
How should patients be managed?

Part IV

Given the diffuse microbleeding secondary to CFE in the case of active hemolysis, patients are advised to perform an emergency exchange with 12 concentrated red blood
cells.
Fever for two days after transfusion, no abnormality
in infectious assessment.
CT angiography of the chest and bifunctional ultrasound of the extremities show acute PE and deep vein thrombosis (DVT) in the middle of the right arm, so anticoagulation therapy
is started.
Ophthalmic evaluation shows scattered "cotton hairs" that support vascular occlusion
.

Although there was no significant improvement at the end of the 4-week hospital stay, repeated electrophoresis showed 88% Hb A, 5% Hb S, and 5% Hb C, for which monthly blood
changes are recommended.
Patients are advised to follow up with trials of dopamine agonist or amantadine therapy to treat exercise incapacitation
.
However, 3 months after the initial visit, the patient died
for unknown reasons.

discuss

Fat embolism syndrome (FES) requires the presence of fat globules in the systemic circulation and recognizable clinical patterns such as respiratory symptoms, petechiae, neurologic signs, fever, hematologic abnormalities, and death
.
This syndrome is usually caused by orthopedic trauma, but can also come from non-traumatic events such as bone marrow necrosis
.
The fat emboli that enter the brain circulation are called brain fat emboli.

Neurologic symptoms of CFE include encephalopathy, ischemic stroke, hemorrhagic stroke, or seizures
.

Sickle cell disease (SCD) may be associated
with FES.
In 81% of cases, FES presents as non-Hb SS SCD, suggesting that bone marrow necrosis and FES are more likely to occur in mild phenotypes of SCD, such as Hb SC
.

Sickle red blood cells may cause avascular necrosis
of the bone marrow.
The pathophysiology of FES has not been fully elucidated, but it is believed that fat microspheres enter the venous circulation
after trauma.
Another theory is biochemical and inflammatory lesions
.
Systemic embolism mechanisms may involve adipose emboluses passing through foramen ovale that are not closed, but are not indicated in this patient
.
FES can have an excessive inflammatory response and high disability and mortality
.
To date, no studies have reported long-term outcomes
of CFE in patients with SCD.

Patients with this Hb SC experienced acute neurocognitive decline
after vascular occlusive crisis.
Tips for us: First, this case may be the only reported motor mutism
caused by CFE in the case of severe neuronal damage.
Important imaging findings of CFE include "starlight" mode on DWI and "walnut kernel" mode
on SWI.
Second, delayed diagnosis leads to delayed blood
exchange.
The SWI sequence may be helpful for early diagnosis because it may be superior to the GRE sequence
in detecting microbleeding.

conclusion

CFE
should be considered in sickle cell patients with acute neurologic symptoms.
SWI is more sensitive and facilitates a clearer diagnosis
.
Delayed blood exchange may affect clinical outcomes
.