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How is the diagnosis and differential diagnosis of sudden changes in mental status in children? Recently, the clinical reasoning series of Neurology reported a case of acute headache, vomiting and confusion in a 7-year-old boy.
Let's take a look at its clinical reasoning process.
This article is published by Yimaitong authorized by the author, please do not reprint without authorization.
Case brief introduction The patient is a 7-year-old boy who presented to the doctor with "emergency headache, vomiting and confusion".
Two months before presentation, the patient had intermittent claudication due to pain in his right thigh.
Three days before admission, the patient had a headache.
Two days before admission, the patient felt fatigue, nausea and vomiting.
Behavior changes, instability, and new palm and sole rash appeared on the day of consultation.
He was subsequently referred for confusion and lethargy.
The patient has no recent weight change, fever, animal contact or travel history.
The previous medical history was mainly facial paralysis caused by HSV infection at the age of 5.
No medication history, no known history of allergies, normal development, vaccination as planned.
The father of the patient had recent gastrointestinal disease, but other contacts were not sick.
Physical examination of the whole body showed drowsiness, irritability, lumps on the right thigh and ecchymosis on the palms.
Neurological examination showed that light touch can be awakened.
Only simple commands can be followed.
Orientation questions can only be answered with "Yes/No", and all naming questions can be answered with "I don't know"; no obvious abnormalities in cranial nerves; muscle volume muscle tone Normal, muscle strength above 3/5; normal light touch, normal sole reflex; no discernibility; able to lie on the bed independently, but refuse to stand or walk. Questions to ponder: 1.
Location diagnosis? 2.
What are the differential diagnoses? Localization and differential diagnosis.
Extensive changes in consciousness are located in the bilateral hemispheres or reticular activation system; compulsive behavior may indicate orbitofrontal/anterior cingulate gyrus involvement; possible aphasia is located in the dominant hemisphere.
Considering acute attacks and multifocality, stroke and infectious meningoencephalitis, focal seizures, intracranial malignant/metastatic tumors, toxic metabolic encephalopathy, and autoimmune/post-infection lesions should be considered.
A plain CT scan of the head showed low signal changes in the right parietal lobe and left occiput with angioedema.
Subsequent cranial MRI/MRA showed acute multifocal infarctions in the bilateral posterior temporal lobe, parietal lobe and left occipital lobe; the left posterior cerebral artery was occluded, and the posterior branch of the left middle cerebral artery was sparse (Figure AC).
Continuous video EEG showed no epileptic activity.
Plain radiographs and MRI of the right thigh suggest that osteosarcoma or Ewing's sarcoma should be considered.
Laboratory examination showed mildly elevated transaminases (AST 116, ALT 78), mild normal cellular anemia (Hgb 10.
5, platelet 145), C-reactive protein (47.
6), ESR (19) and LDH (1336) were elevated; No obvious abnormalities in metabolism, endocrine, urine or blood coagulation; no abnormality in cerebrospinal fluid; no abnormality in heart rhythm/conduction.
Transesophageal echocardiography revealed a pedicled mass (5.
5×5.
0mm) of the mitral valve, accompanied by mild To moderate reflux.
Figure the patient's head imaging data and pathological results.
A) DWI on the first day of hospitalization showed limited diffusion in the left temporal parietal lobe and left occipital lobe, consistent with acute infarction; B) The initial SWI did not show any hemorrhagic transformation.
C) MRA shows occlusion of the P2 segment of the left posterior cerebral artery (arrow), and the posterior branch of the left MCA is sparse.
D) The head CT scan on the 7th day of hospitalization showed that the infarct progress was accompanied by extensive bilateral cerebral edema, obvious space-occupying effect, and brain herniation.
E) The H&E staining (×200) of the right femoral mass showed consistent with high-grade sarcoma, possibly osteosarcoma.
F) H&E staining (×40) of acute cerebellar microinfarcts shows infarction.
G) H&E staining of mitral valve neoplasms (×100) shows lamellar fibrin (eosinophilic substance) and some platelets with a small number of white blood cells in between, consistent with fibrin thrombus.
Questions to ponder: 1.
What other inspections are required? Further examination of multifocal stroke, sarcoma, and cardiac neoplasms requires testing for infection, coagulopathy, and malignant complications [such as tumor embolism, non-bacterial thrombotic endocarditis (NBTE)].
The blood culture was negative.
Although the patient had no fever and leukocytosis, he received empirical antimicrobial therapy (acyclovir, vancomycin study ceftriaxone).
Both Bartonella and Bernardella were negative for serology.
CSF Gram stain/culture was negative, PCR for enterovirus, EV virus, HSV and VZV were all negative; blood coagulation examination showed no obvious abnormality; biopsy of the right femur showed osteosarcoma (Figure E).
CT-based staging showed no metastasis or lymphadenopathy, but showed multifocal splenic and renal infarction.
Questions to ponder: 1.
What are the possible treatment options? 2.
What factors limit treatment options? Treatment After evaluating and treating possible infections, treatment for stroke, possible NBTE, and potential intracranial pressure (ICP) increase should also be considered.
The patient is not within the thrombolysis or thrombectomy window.
Therefore, secondary stroke prevention should be considered.
On the second day of hospitalization, the multidisciplinary team weighed the risks/benefits of cardiac surgery to remove cardiac vegetation, and concluded that in the absence of clear recurrent thromboembolic events or severe valve/heart dysfunction, the risks of surgery outweigh the benefits.
Therefore, NBTE requires anticoagulation therapy.
Edema caused by a large infarct can lead to an increase in ICP.
On the 3rd day of hospitalization, the patient had transient pupil unequal size, prompting the need to lower ICP.
Re-examination of CT showed a new right frontal infarction.
In order to better manage the ICP, the patient installed an epidural bolt monitor.
On the 6th day of hospitalization, the patient developed a new left cerebellar infarction and needed pentobarbital to induce coma due to elevated ICP.
In the end, the patient had a brain herniation (Figure D) due to the continuous increase of ICP and eventually died.
Autopsy revealed tan, fibrous, fragile mitral valve neoplasms (1.
0×0.
4×0.
3cm); 8 cm mass on the distal right femur; diffuse cerebral edema with multiple infarcts; brain histological examination showed no tumor embolism Signs (figure F); kidney sections show fibrin thromboembolism, which has the same histological structure as cardiac neoplasms (figure G).
Discussion In developed countries, the incidence of stroke in children is estimated to be 1.
0-2.
0 per 100,000 people per year.
The main clinical manifestations are focal dysfunction, but there are also non-focal symptoms, such as headaches, changes in mental status, and seizures, which affect the diagnosis.
The main causes are arterial disease and heart embolism, followed by hematology (such as thrombosis or sickle cell), inflammatory/infectious and genetic/metabolic causes.
Stroke management is mainly based on adult evidence, but the guidelines recommend that children with adult standards should consider thrombolysis and endovascular intervention; the guidelines also recommend decompression.
NBTE is an extremely rare cause of stroke in children.
NBTE was found in 0.
3-9.
3% (mean 1.
3%) in autopsy, but only 3-4% of NBTE cases were children aged 0-19 years.
The highest risk factors for NBTE are malignant tumors, especially adenocarcinoma, and acute diseases such as sepsis or burns.
The treatment of NBTE mainly uses unfractionated heparin or low molecular weight heparin for anticoagulation therapy.
Warfarin is generally not recommended for coagulopathy associated with malignant tumors.
As with all recent strokes, anticoagulation therapy must consider the potential risk of intracranial hemorrhage.
Adult data show that after confirming that there is no hemorrhagic transformation (HT), anticoagulation can be started a few days after a small/moderate infarction, and anticoagulation usually starts several weeks after a major stroke.
If anticoagulation therapy fails, surgery may prevent further embolic events.
Early cardiac surgery is suitable for recurrent embolism, as well as continuous enlargement of neoplasms, severe reflux, and large (> 10mm) active neoplasms despite proper treatment.
However, surgery requires active anticoagulation therapy, so large-scale infarction is often contraindicated.
This case provides many important teaching points for adult and pediatric neurologists.
First of all, childhood stroke is an important cause of acute neurological changes in children.
Clinicians should be aware that children with stroke may have non-specific changes, such as changes in mental status.
Secondly, there are many causes of stroke in children, but heart embolism should always be considered.
Third, NBTE patients may suffer from a variety of thromboembolic complications.
References: Gregory J.
Wong, Cristina M.
Gaudioso, Eleanor Castro, et al.
Clinical Reasoning: A 7-year-Old Boy with Acute Onset Altered Mental Status.
Neurology published online April 13, 2021.
DOI 10.
1212/WNL.
0000000000012034 .
Let's take a look at its clinical reasoning process.
This article is published by Yimaitong authorized by the author, please do not reprint without authorization.
Case brief introduction The patient is a 7-year-old boy who presented to the doctor with "emergency headache, vomiting and confusion".
Two months before presentation, the patient had intermittent claudication due to pain in his right thigh.
Three days before admission, the patient had a headache.
Two days before admission, the patient felt fatigue, nausea and vomiting.
Behavior changes, instability, and new palm and sole rash appeared on the day of consultation.
He was subsequently referred for confusion and lethargy.
The patient has no recent weight change, fever, animal contact or travel history.
The previous medical history was mainly facial paralysis caused by HSV infection at the age of 5.
No medication history, no known history of allergies, normal development, vaccination as planned.
The father of the patient had recent gastrointestinal disease, but other contacts were not sick.
Physical examination of the whole body showed drowsiness, irritability, lumps on the right thigh and ecchymosis on the palms.
Neurological examination showed that light touch can be awakened.
Only simple commands can be followed.
Orientation questions can only be answered with "Yes/No", and all naming questions can be answered with "I don't know"; no obvious abnormalities in cranial nerves; muscle volume muscle tone Normal, muscle strength above 3/5; normal light touch, normal sole reflex; no discernibility; able to lie on the bed independently, but refuse to stand or walk. Questions to ponder: 1.
Location diagnosis? 2.
What are the differential diagnoses? Localization and differential diagnosis.
Extensive changes in consciousness are located in the bilateral hemispheres or reticular activation system; compulsive behavior may indicate orbitofrontal/anterior cingulate gyrus involvement; possible aphasia is located in the dominant hemisphere.
Considering acute attacks and multifocality, stroke and infectious meningoencephalitis, focal seizures, intracranial malignant/metastatic tumors, toxic metabolic encephalopathy, and autoimmune/post-infection lesions should be considered.
A plain CT scan of the head showed low signal changes in the right parietal lobe and left occiput with angioedema.
Subsequent cranial MRI/MRA showed acute multifocal infarctions in the bilateral posterior temporal lobe, parietal lobe and left occipital lobe; the left posterior cerebral artery was occluded, and the posterior branch of the left middle cerebral artery was sparse (Figure AC).
Continuous video EEG showed no epileptic activity.
Plain radiographs and MRI of the right thigh suggest that osteosarcoma or Ewing's sarcoma should be considered.
Laboratory examination showed mildly elevated transaminases (AST 116, ALT 78), mild normal cellular anemia (Hgb 10.
5, platelet 145), C-reactive protein (47.
6), ESR (19) and LDH (1336) were elevated; No obvious abnormalities in metabolism, endocrine, urine or blood coagulation; no abnormality in cerebrospinal fluid; no abnormality in heart rhythm/conduction.
Transesophageal echocardiography revealed a pedicled mass (5.
5×5.
0mm) of the mitral valve, accompanied by mild To moderate reflux.
Figure the patient's head imaging data and pathological results.
A) DWI on the first day of hospitalization showed limited diffusion in the left temporal parietal lobe and left occipital lobe, consistent with acute infarction; B) The initial SWI did not show any hemorrhagic transformation.
C) MRA shows occlusion of the P2 segment of the left posterior cerebral artery (arrow), and the posterior branch of the left MCA is sparse.
D) The head CT scan on the 7th day of hospitalization showed that the infarct progress was accompanied by extensive bilateral cerebral edema, obvious space-occupying effect, and brain herniation.
E) The H&E staining (×200) of the right femoral mass showed consistent with high-grade sarcoma, possibly osteosarcoma.
F) H&E staining (×40) of acute cerebellar microinfarcts shows infarction.
G) H&E staining of mitral valve neoplasms (×100) shows lamellar fibrin (eosinophilic substance) and some platelets with a small number of white blood cells in between, consistent with fibrin thrombus.
Questions to ponder: 1.
What other inspections are required? Further examination of multifocal stroke, sarcoma, and cardiac neoplasms requires testing for infection, coagulopathy, and malignant complications [such as tumor embolism, non-bacterial thrombotic endocarditis (NBTE)].
The blood culture was negative.
Although the patient had no fever and leukocytosis, he received empirical antimicrobial therapy (acyclovir, vancomycin study ceftriaxone).
Both Bartonella and Bernardella were negative for serology.
CSF Gram stain/culture was negative, PCR for enterovirus, EV virus, HSV and VZV were all negative; blood coagulation examination showed no obvious abnormality; biopsy of the right femur showed osteosarcoma (Figure E).
CT-based staging showed no metastasis or lymphadenopathy, but showed multifocal splenic and renal infarction.
Questions to ponder: 1.
What are the possible treatment options? 2.
What factors limit treatment options? Treatment After evaluating and treating possible infections, treatment for stroke, possible NBTE, and potential intracranial pressure (ICP) increase should also be considered.
The patient is not within the thrombolysis or thrombectomy window.
Therefore, secondary stroke prevention should be considered.
On the second day of hospitalization, the multidisciplinary team weighed the risks/benefits of cardiac surgery to remove cardiac vegetation, and concluded that in the absence of clear recurrent thromboembolic events or severe valve/heart dysfunction, the risks of surgery outweigh the benefits.
Therefore, NBTE requires anticoagulation therapy.
Edema caused by a large infarct can lead to an increase in ICP.
On the 3rd day of hospitalization, the patient had transient pupil unequal size, prompting the need to lower ICP.
Re-examination of CT showed a new right frontal infarction.
In order to better manage the ICP, the patient installed an epidural bolt monitor.
On the 6th day of hospitalization, the patient developed a new left cerebellar infarction and needed pentobarbital to induce coma due to elevated ICP.
In the end, the patient had a brain herniation (Figure D) due to the continuous increase of ICP and eventually died.
Autopsy revealed tan, fibrous, fragile mitral valve neoplasms (1.
0×0.
4×0.
3cm); 8 cm mass on the distal right femur; diffuse cerebral edema with multiple infarcts; brain histological examination showed no tumor embolism Signs (figure F); kidney sections show fibrin thromboembolism, which has the same histological structure as cardiac neoplasms (figure G).
Discussion In developed countries, the incidence of stroke in children is estimated to be 1.
0-2.
0 per 100,000 people per year.
The main clinical manifestations are focal dysfunction, but there are also non-focal symptoms, such as headaches, changes in mental status, and seizures, which affect the diagnosis.
The main causes are arterial disease and heart embolism, followed by hematology (such as thrombosis or sickle cell), inflammatory/infectious and genetic/metabolic causes.
Stroke management is mainly based on adult evidence, but the guidelines recommend that children with adult standards should consider thrombolysis and endovascular intervention; the guidelines also recommend decompression.
NBTE is an extremely rare cause of stroke in children.
NBTE was found in 0.
3-9.
3% (mean 1.
3%) in autopsy, but only 3-4% of NBTE cases were children aged 0-19 years.
The highest risk factors for NBTE are malignant tumors, especially adenocarcinoma, and acute diseases such as sepsis or burns.
The treatment of NBTE mainly uses unfractionated heparin or low molecular weight heparin for anticoagulation therapy.
Warfarin is generally not recommended for coagulopathy associated with malignant tumors.
As with all recent strokes, anticoagulation therapy must consider the potential risk of intracranial hemorrhage.
Adult data show that after confirming that there is no hemorrhagic transformation (HT), anticoagulation can be started a few days after a small/moderate infarction, and anticoagulation usually starts several weeks after a major stroke.
If anticoagulation therapy fails, surgery may prevent further embolic events.
Early cardiac surgery is suitable for recurrent embolism, as well as continuous enlargement of neoplasms, severe reflux, and large (> 10mm) active neoplasms despite proper treatment.
However, surgery requires active anticoagulation therapy, so large-scale infarction is often contraindicated.
This case provides many important teaching points for adult and pediatric neurologists.
First of all, childhood stroke is an important cause of acute neurological changes in children.
Clinicians should be aware that children with stroke may have non-specific changes, such as changes in mental status.
Secondly, there are many causes of stroke in children, but heart embolism should always be considered.
Third, NBTE patients may suffer from a variety of thromboembolic complications.
References: Gregory J.
Wong, Cristina M.
Gaudioso, Eleanor Castro, et al.
Clinical Reasoning: A 7-year-Old Boy with Acute Onset Altered Mental Status.
Neurology published online April 13, 2021.
DOI 10.
1212/WNL.
0000000000012034 .
