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*It is only for medical professionals to read for reference.
Will you miss this disease? White matter lesions of the central nervous system are a large class of heterogeneous diseases, and the clinical diagnosis and treatment process is full of challenges.
Dr.
Jiao Bin, Department of Neurology, Xiangya Hospital of Central South University, brought us a rare case with multiple clinical manifestations.
Suspected patient with Behcet's disease, 28 years old, Han nationality, married, was admitted to the hospital for "recurrent oral ulcers for more than 2 years, slurred speech and weakness of limbs for 9 months".
In January 2018, the patient had repeated oral ulcers with no obvious cause, at least 3 times a year, and each time lasted for more than 1 week, he could get better on his own.
In July 2019, the patient developed genital pruritus and scratches, which appeared twice a year and improved on its own.
In January 2020, the patient gradually appeared slurred speech, weak limbs, obvious left side, lower limbs heavier than upper limbs, need to support walking, accompanied by numbness of limbs, affecting daily activities.
In April 2020, the patient went to the Department of Neurology of Hunan Brain Hospital.
MRI of the head revealed multiple abnormal signal foci in the right basal ganglia, bilateral paraventricular, right frontal lobe, and corpus callosum (Figure 1); cerebrospinal fluid routine, biochemical and prolapse Myelin antibodies and oligoclonal zones are not abnormal, and multiple sclerosis may be considered.
After being treated with prednisone 50 mg po qd, the symptoms of limb fatigue improved, and the drug was discontinued after 1 month of discharge to 25 mg po qd.
Figure 1: The patient's brain MRI in April 2020 (picture from Dr Jiao Bin's PPT) In June 2020, the patient's left limb weakness and slurred speech symptoms once again worsened.
Came to the neurology clinic of our hospital, and re-examination of the head MRI showed that there are multiple abnormal signal lesions in the double frontal parietal lobe, lateral ventricle, corpus callosum pressure, and right basal ganglia: demyelinating disease? Neural Behcet is waiting to be drained (Figure 2).
To continue oral hormone therapy, it is recommended to see a rheumatology department.
Figure 2: The patient's brain MRI in June 2020 (picture from Dr.
Jiao Bin's PPT) The patient has had no fever, decreased vision, skin rash, joint pain, abdominal pain, diarrhea, etc.
since the onset of illness.
Since the onset of the disease, diet and sleep are acceptable, and the two stools are normal.
Past history: Two cesarean sections in 2013 and 2016, history of hepatitis B.
Personal history is indistinguishable.
Marriage and childbirth history: married at the age of 20 and have 2 children.
The husband and children are in good health.
Menstrual history: 13-year-old menarche, 4 days/30 days, the amount is available, the time of the most recent menstrual period is 20 July 18
Family history: The parents are alive, and the patient's grandfather and grandmother are married to close relatives (cousins).
The patient was admitted to the Department of Rheumatology and Immunology on July 28, 2020.
General physical examination: T 36.
7°C, P 104 times/min, R 20 times/min, BP 123/82mmHg, superficial lymph nodes all over the body, full moon face, no cyanosis of lips, 3 ulcers in the mouth, ulcer area 2mm *Approximately 2mm, with the tongue out in the middle.
The neck is soft, the heart, lungs, abdomen (-), a small amount of scars on the vulva, and no obvious ulcers.
Nervous system examination: Consciousness, mild dysarthria, normal memory, comprehension, and calculation ability, bilateral pupils with a 3mm equal circle, sensitive to light reflection, and no abnormalities in the remaining cranial nerves.
The left upper limb muscle strength is 3+, the left lower limb muscle strength is 2+, the right upper and lower limb muscle strength is 5, the left limb muscle tension is slightly higher, and the remaining limb muscle tension is normal.
The left tendon reflex is slightly active.
It feels normal.
The Pap sign on the left is positive, and the Pap sign on the right is negative.
Meningeal irritation was negative.
▌ Case summary: The patient is a young female, with an insidious onset, a chronic course, and progressive development, with no special history.
The positive signs of the nervous system are slightly slurred speech, weakness on the left side, and pathological signs on the left side (+).
Combined with brain imaging, there are multiple abnormal signal foci in the brain.
The patient's positioning diagnosis considers positioning in the central nervous system.
And the patient has oral and vulvar ulcers, suggesting that there are multiple systems involved.
In terms of treatment, the patient's symptoms of hormone therapy improved slightly, but not significantly.
Overall analysis, according to the midnight principle, the qualitative diagnosis of patients needs to consider inflammatory lesions, genetic lesions, metabolic lesions, tumors and infectious lesions, and they need to be checked one by one.
▌ Auxiliary examination: After the patient was admitted to the hospital, the auxiliary examination was completed.
The main positive result is shown in Figure 3, indicating that the patient has iron deficiency anemia.
In July 2020, the cerebrovascular MRA and cranial MRI were reviewed again (Figure 4).
There were no cerebrovascular abnormalities in the cranial MRA.
Compared with June (Figure 2), the lesion was still limited to the bilateral frontal and parietal lobes.
, Lateral ventricle, corpus callosum, and right basal ganglia area.
The other auxiliary examination results have no clear clinical guiding significance.
Figure 3: The patient’s auxiliary examination and positive results (picture from Dr.
Jiao Bin’s PPT) Figure 4: The patient’s July brain MRI re-examination (picture from Dr.
Jiao Bin’s PPT) after a multidisciplinary consultation, considering the possibility of the patient’s neurological Behcet, The preliminary diagnosis is as follows: 1.
Behcet's disease? 2.
Intracranial lesions: Neural Behcet? Demyelinating encephalopathy? 3.
Moderate anemia 4.
Viral hepatitis B 5.
Postoperative state (cesarean section) The patient was given hormone shock therapy and immunosuppressive therapy for more than one month.
However, the patient's limb weakness symptoms aggravated, his left muscle strength was grade 1, and his speech ambiguity symptoms aggravated.
The patient was admitted to the hospital again in September 2020.
After admission, the brain MRI was reviewed (Figure 5).
Compared with the July brain MRI (Figure 4), the area of multiple abnormal signal lesions in the double frontal parietal lobe, lateral ventricle, corpus callosum pressure, and right basal ganglia area was enlarged than before.
, The enhancement is not significantly enhanced.
Upon admission this time, the patient was given hormone shock and immunosuppressive therapy again, but the patient's symptoms still did not improve.
Figure 5: The patient’s September MRI (picture from Dr.
Jiao Bin’s PPT) is full of doubts.
Reviewing the patient’s diagnosis and treatment, we can find the following doubts about the diagnosis of neurobehcet: 1.
ESR, low C-reactive protein, and normal cerebrospinal fluid 2.
Hormones Poor effect with immunosuppressive agents.
3.
There is no improvement in imaging lesions.
We should consider whether the diagnosis of intracranial lesions is correct.
Let us review the relevant knowledge of Behcet's disease.
Behcet's disease is a rare chronic systemic vascular inflammatory disease, which mainly manifests as recurrent oral ulcers, genital ulcers, skin and eye damage, and can involve joints, blood vessels, digestive tracts, nerves and other systems throughout the body.
The diagnostic criteria for Behcet's disease and neurobehcet are shown in Figure 6.
In the diagnostic criteria, neurobehcet needs at least one of neuroimaging and (or cerebrospinal fluid) characteristic abnormalities (Figure 7).
Combined with the patient's performance, the patient does not meet the diagnostic criteria for Behcet's disease, and can only meet the probable neuro Behcet.
Figure 6: Diagnostic criteria for Behcet's disease (picture from Dr.
Jiao Bin's PPT) Figure 7: Neuroimaging and characteristic abnormalities of cerebrospinal fluid (picture from Dr.
Jiao Bin's PPT) The patients with peak circulation have further improved the MRS of craniocerebral magnetic resonance spectroscopy analysis (Magnetic Resonance Spectroscopy, MRS): MRS indicates that the NAA peak (N-acetyl aspartic acid, NAA, N-acetyl aspartic acid) in the abnormal signal area of the right frontal and parietal lobe is reduced, and the Cr peak (creatine, Cr, creatine) is slightly reduced.
Decrease, Cho (Choline, Cho, Choline) increases, and Lac (lactate, Lac, lactic acid) peaks are visible.
Combined with genetic testing, the possibility of hereditary metabolic encephalopathy and hereditary leukoencephalopathy is ruled out.
Thus, the patient underwent whole-exome sequencing.
The results suggest that the patient has colony-stimulating factor 1 receptor (CSF1R) gene c.
2381T>C; p.
I794T mutation, ACMG interpretation (ACMG, American College of Medical Genetics and Genomics, American College of Medical Genetics and Genomics) The Institute of Genomics and Genomics) suggested that the mutation is pathogenic.
It is a previously reported pathogenic site mutation.
The disease caused is hereditary diffuse leukoencephalopathy with spheroid (HDLS).
Let us take a look at HDLS together.
HDLS was first reported since 1984 and was inherited in an autosomal dominant manner.
2011 cloned the pathogenic gene CSF1R caused by mutations.
More than 120 cases of CSF1R gene mutation have been reported worldwide, most of which are from Japan.
So far, 80 mutations in the CSF1R gene have been reported, almost all of which are located in the tyrosine kinase domain (Figure 8), which can cause the proliferation and differentiation of microglia to be blocked.
Abnormal microglia in the adult brain play a key role in white matter degeneration, leading to primary axonal disease (axonal globular degeneration) and secondary demyelinating disease.
Figure 8: CSF1R gene and tyrosine kinase domain (picture from Dr.
Jiao Bin's PPT) The average age of onset of HDLS is 43 years old (18-78 years old are reported), female patients have an earlier age of onset than men, 95% of cases 60 Symptoms appear before age.
The clinical phenotypes of HDLS are as follows: Progressive cognitive decline (87%) Affective disorders: depression, apathy, anxiety, irritability (55%) Behavior changes Parkinson-like symptoms: namely tremor, stiffness, slow movement and postural instability ) (41%) pyramidal tract signs (such as hyperreflexia, spasms) bulbar signs (such as dysarthria, dysphagia) ataxia seizures (33%) In addition, patients may have multiple system symptoms, including bone changes, Premature ovarian failure and psoriasis, but there are no reports of ulcers.
HDLS imaging manifestations are divided into four types: (1) White matter lesions: can appear before symptoms, usually involving bilateral, not necessarily symmetrical, gradually fusing from a sheet, mainly distributed in the frontal lobe and parietal lobe.
The projection fibers are involved, including the pyramidal tracts in the internal capsule and brainstem, and U-shaped fibers can be involved in the end-stage of the disease.
It can be seen that the DWI high signal in the white matter lasts for several months.
Enhanced scan without enhancement.
In this case, the patient’s imaging showed typical white matter lesions.
(2) Brain atrophy: As the disease progresses, the frontal and parietal cortex shrinks.
(3) Thinning of the corpus callosum (4) Calcification in white matter: Calcification is generally distributed in the white matter of the frontal lobe adjacent to the anterior horn of the lateral ventricle.
A small probability occurs in the subparietal cortex white matter.
Calcification in the area around the bilateral frontal corpus callosum is called a stepping stone appearance (Figure 9).
Figure 9: HDLS white matter calcification (picture from Doctor Jiao Bin's PPT) CSF1R gene c.
2381T>C mutation has been reported in 7 cases worldwide, as shown in Figure 10.
The ratio of male to female is similar.
The youngest age of onset is 28 years old and the oldest is 60 years old.
In terms of the first symptoms, the younger the age, the first symptom is dyskinesia, while in the case of older people, cognitive impairment is the first symptom, which may be accompanied by other symptoms.
The performance of this patient has not been reported.
Figure 10: The currently reported c.
2381T>C mutation (picture from Dr.
Jiao Bin's PPT) traced the source and further sequenced the patient’s father and mother to determine whether the patient’s mutation came from the father or the mother.
In the end, it was found that the patient's mutation came from the mother (Figure 11).
So the patient's mother was followed up.
The patient's mother is 54 years old and has a third-grade education level in elementary school.
His memory has declined for more than 10 years, his calculation ability has decreased slightly, and he can take care of himself in work and daily life.
I usually feel unhappy, worried and afraid, have been diagnosed with depression in the past, and have not taken medication regularly.
Neuropsychological assessment of the patient’s mother: MMSE (Mini-Mental State Examination): 18 points; MoCA (Montreal Cognitive Assessment): 11 points; AVLT (auditory verbal learning task, auditory Vocabulary Learning Test): 72 points.
The patient's mother has manifestations of cognitive decline.
The brain magnetic resonance of the patient's mother showed multiple white matter lesions.
Figure 11: Family verification (picture from Doctor Jiao Bin's PPT) There is currently no specific treatment for HDLS.
Because the CSF1R mutation affects the function of microglia, hematopoietic stem cell transplantation may have a therapeutic effect on the disease.
Symptomatic treatment includes: Parkinson's phenotype can try drugs such as levodopa, but the effect is not good; depression symptoms can try antidepressant drugs, but the long-term benefit is small; psychotic symptoms (aggressive behavior) can use antipsychotic drugs; Epilepsy medications should be started in any individual with seizures.
Summary: 1.
Neural Behcet is an exclusive diagnosis, especially when the treatment effect of hormones and immunosuppressants is poor, the diagnosis should be made with caution.
2.
There are many types of diseases related to white matter lesions, and comprehensive consideration should be given to clinical qualitative diagnosis.
3.
The clinical phenotype of HDLS patients is very heterogeneous, not only involving the central nervous system, but also involving multiple systems throughout the body.
4.
Inherited disease ≠ no cure, HDLS may be effective for bone marrow transplantation.
Will you miss this disease? White matter lesions of the central nervous system are a large class of heterogeneous diseases, and the clinical diagnosis and treatment process is full of challenges.
Dr.
Jiao Bin, Department of Neurology, Xiangya Hospital of Central South University, brought us a rare case with multiple clinical manifestations.
Suspected patient with Behcet's disease, 28 years old, Han nationality, married, was admitted to the hospital for "recurrent oral ulcers for more than 2 years, slurred speech and weakness of limbs for 9 months".
In January 2018, the patient had repeated oral ulcers with no obvious cause, at least 3 times a year, and each time lasted for more than 1 week, he could get better on his own.
In July 2019, the patient developed genital pruritus and scratches, which appeared twice a year and improved on its own.
In January 2020, the patient gradually appeared slurred speech, weak limbs, obvious left side, lower limbs heavier than upper limbs, need to support walking, accompanied by numbness of limbs, affecting daily activities.
In April 2020, the patient went to the Department of Neurology of Hunan Brain Hospital.
MRI of the head revealed multiple abnormal signal foci in the right basal ganglia, bilateral paraventricular, right frontal lobe, and corpus callosum (Figure 1); cerebrospinal fluid routine, biochemical and prolapse Myelin antibodies and oligoclonal zones are not abnormal, and multiple sclerosis may be considered.
After being treated with prednisone 50 mg po qd, the symptoms of limb fatigue improved, and the drug was discontinued after 1 month of discharge to 25 mg po qd.
Figure 1: The patient's brain MRI in April 2020 (picture from Dr Jiao Bin's PPT) In June 2020, the patient's left limb weakness and slurred speech symptoms once again worsened.
Came to the neurology clinic of our hospital, and re-examination of the head MRI showed that there are multiple abnormal signal lesions in the double frontal parietal lobe, lateral ventricle, corpus callosum pressure, and right basal ganglia: demyelinating disease? Neural Behcet is waiting to be drained (Figure 2).
To continue oral hormone therapy, it is recommended to see a rheumatology department.
Figure 2: The patient's brain MRI in June 2020 (picture from Dr.
Jiao Bin's PPT) The patient has had no fever, decreased vision, skin rash, joint pain, abdominal pain, diarrhea, etc.
since the onset of illness.
Since the onset of the disease, diet and sleep are acceptable, and the two stools are normal.
Past history: Two cesarean sections in 2013 and 2016, history of hepatitis B.
Personal history is indistinguishable.
Marriage and childbirth history: married at the age of 20 and have 2 children.
The husband and children are in good health.
Menstrual history: 13-year-old menarche, 4 days/30 days, the amount is available, the time of the most recent menstrual period is 20 July 18
Family history: The parents are alive, and the patient's grandfather and grandmother are married to close relatives (cousins).
The patient was admitted to the Department of Rheumatology and Immunology on July 28, 2020.
General physical examination: T 36.
7°C, P 104 times/min, R 20 times/min, BP 123/82mmHg, superficial lymph nodes all over the body, full moon face, no cyanosis of lips, 3 ulcers in the mouth, ulcer area 2mm *Approximately 2mm, with the tongue out in the middle.
The neck is soft, the heart, lungs, abdomen (-), a small amount of scars on the vulva, and no obvious ulcers.
Nervous system examination: Consciousness, mild dysarthria, normal memory, comprehension, and calculation ability, bilateral pupils with a 3mm equal circle, sensitive to light reflection, and no abnormalities in the remaining cranial nerves.
The left upper limb muscle strength is 3+, the left lower limb muscle strength is 2+, the right upper and lower limb muscle strength is 5, the left limb muscle tension is slightly higher, and the remaining limb muscle tension is normal.
The left tendon reflex is slightly active.
It feels normal.
The Pap sign on the left is positive, and the Pap sign on the right is negative.
Meningeal irritation was negative.
▌ Case summary: The patient is a young female, with an insidious onset, a chronic course, and progressive development, with no special history.
The positive signs of the nervous system are slightly slurred speech, weakness on the left side, and pathological signs on the left side (+).
Combined with brain imaging, there are multiple abnormal signal foci in the brain.
The patient's positioning diagnosis considers positioning in the central nervous system.
And the patient has oral and vulvar ulcers, suggesting that there are multiple systems involved.
In terms of treatment, the patient's symptoms of hormone therapy improved slightly, but not significantly.
Overall analysis, according to the midnight principle, the qualitative diagnosis of patients needs to consider inflammatory lesions, genetic lesions, metabolic lesions, tumors and infectious lesions, and they need to be checked one by one.
▌ Auxiliary examination: After the patient was admitted to the hospital, the auxiliary examination was completed.
The main positive result is shown in Figure 3, indicating that the patient has iron deficiency anemia.
In July 2020, the cerebrovascular MRA and cranial MRI were reviewed again (Figure 4).
There were no cerebrovascular abnormalities in the cranial MRA.
Compared with June (Figure 2), the lesion was still limited to the bilateral frontal and parietal lobes.
, Lateral ventricle, corpus callosum, and right basal ganglia area.
The other auxiliary examination results have no clear clinical guiding significance.
Figure 3: The patient’s auxiliary examination and positive results (picture from Dr.
Jiao Bin’s PPT) Figure 4: The patient’s July brain MRI re-examination (picture from Dr.
Jiao Bin’s PPT) after a multidisciplinary consultation, considering the possibility of the patient’s neurological Behcet, The preliminary diagnosis is as follows: 1.
Behcet's disease? 2.
Intracranial lesions: Neural Behcet? Demyelinating encephalopathy? 3.
Moderate anemia 4.
Viral hepatitis B 5.
Postoperative state (cesarean section) The patient was given hormone shock therapy and immunosuppressive therapy for more than one month.
However, the patient's limb weakness symptoms aggravated, his left muscle strength was grade 1, and his speech ambiguity symptoms aggravated.
The patient was admitted to the hospital again in September 2020.
After admission, the brain MRI was reviewed (Figure 5).
Compared with the July brain MRI (Figure 4), the area of multiple abnormal signal lesions in the double frontal parietal lobe, lateral ventricle, corpus callosum pressure, and right basal ganglia area was enlarged than before.
, The enhancement is not significantly enhanced.
Upon admission this time, the patient was given hormone shock and immunosuppressive therapy again, but the patient's symptoms still did not improve.
Figure 5: The patient’s September MRI (picture from Dr.
Jiao Bin’s PPT) is full of doubts.
Reviewing the patient’s diagnosis and treatment, we can find the following doubts about the diagnosis of neurobehcet: 1.
ESR, low C-reactive protein, and normal cerebrospinal fluid 2.
Hormones Poor effect with immunosuppressive agents.
3.
There is no improvement in imaging lesions.
We should consider whether the diagnosis of intracranial lesions is correct.
Let us review the relevant knowledge of Behcet's disease.
Behcet's disease is a rare chronic systemic vascular inflammatory disease, which mainly manifests as recurrent oral ulcers, genital ulcers, skin and eye damage, and can involve joints, blood vessels, digestive tracts, nerves and other systems throughout the body.
The diagnostic criteria for Behcet's disease and neurobehcet are shown in Figure 6.
In the diagnostic criteria, neurobehcet needs at least one of neuroimaging and (or cerebrospinal fluid) characteristic abnormalities (Figure 7).
Combined with the patient's performance, the patient does not meet the diagnostic criteria for Behcet's disease, and can only meet the probable neuro Behcet.
Figure 6: Diagnostic criteria for Behcet's disease (picture from Dr.
Jiao Bin's PPT) Figure 7: Neuroimaging and characteristic abnormalities of cerebrospinal fluid (picture from Dr.
Jiao Bin's PPT) The patients with peak circulation have further improved the MRS of craniocerebral magnetic resonance spectroscopy analysis (Magnetic Resonance Spectroscopy, MRS): MRS indicates that the NAA peak (N-acetyl aspartic acid, NAA, N-acetyl aspartic acid) in the abnormal signal area of the right frontal and parietal lobe is reduced, and the Cr peak (creatine, Cr, creatine) is slightly reduced.
Decrease, Cho (Choline, Cho, Choline) increases, and Lac (lactate, Lac, lactic acid) peaks are visible.
Combined with genetic testing, the possibility of hereditary metabolic encephalopathy and hereditary leukoencephalopathy is ruled out.
Thus, the patient underwent whole-exome sequencing.
The results suggest that the patient has colony-stimulating factor 1 receptor (CSF1R) gene c.
2381T>C; p.
I794T mutation, ACMG interpretation (ACMG, American College of Medical Genetics and Genomics, American College of Medical Genetics and Genomics) The Institute of Genomics and Genomics) suggested that the mutation is pathogenic.
It is a previously reported pathogenic site mutation.
The disease caused is hereditary diffuse leukoencephalopathy with spheroid (HDLS).
Let us take a look at HDLS together.
HDLS was first reported since 1984 and was inherited in an autosomal dominant manner.
2011 cloned the pathogenic gene CSF1R caused by mutations.
More than 120 cases of CSF1R gene mutation have been reported worldwide, most of which are from Japan.
So far, 80 mutations in the CSF1R gene have been reported, almost all of which are located in the tyrosine kinase domain (Figure 8), which can cause the proliferation and differentiation of microglia to be blocked.
Abnormal microglia in the adult brain play a key role in white matter degeneration, leading to primary axonal disease (axonal globular degeneration) and secondary demyelinating disease.
Figure 8: CSF1R gene and tyrosine kinase domain (picture from Dr.
Jiao Bin's PPT) The average age of onset of HDLS is 43 years old (18-78 years old are reported), female patients have an earlier age of onset than men, 95% of cases 60 Symptoms appear before age.
The clinical phenotypes of HDLS are as follows: Progressive cognitive decline (87%) Affective disorders: depression, apathy, anxiety, irritability (55%) Behavior changes Parkinson-like symptoms: namely tremor, stiffness, slow movement and postural instability ) (41%) pyramidal tract signs (such as hyperreflexia, spasms) bulbar signs (such as dysarthria, dysphagia) ataxia seizures (33%) In addition, patients may have multiple system symptoms, including bone changes, Premature ovarian failure and psoriasis, but there are no reports of ulcers.
HDLS imaging manifestations are divided into four types: (1) White matter lesions: can appear before symptoms, usually involving bilateral, not necessarily symmetrical, gradually fusing from a sheet, mainly distributed in the frontal lobe and parietal lobe.
The projection fibers are involved, including the pyramidal tracts in the internal capsule and brainstem, and U-shaped fibers can be involved in the end-stage of the disease.
It can be seen that the DWI high signal in the white matter lasts for several months.
Enhanced scan without enhancement.
In this case, the patient’s imaging showed typical white matter lesions.
(2) Brain atrophy: As the disease progresses, the frontal and parietal cortex shrinks.
(3) Thinning of the corpus callosum (4) Calcification in white matter: Calcification is generally distributed in the white matter of the frontal lobe adjacent to the anterior horn of the lateral ventricle.
A small probability occurs in the subparietal cortex white matter.
Calcification in the area around the bilateral frontal corpus callosum is called a stepping stone appearance (Figure 9).
Figure 9: HDLS white matter calcification (picture from Doctor Jiao Bin's PPT) CSF1R gene c.
2381T>C mutation has been reported in 7 cases worldwide, as shown in Figure 10.
The ratio of male to female is similar.
The youngest age of onset is 28 years old and the oldest is 60 years old.
In terms of the first symptoms, the younger the age, the first symptom is dyskinesia, while in the case of older people, cognitive impairment is the first symptom, which may be accompanied by other symptoms.
The performance of this patient has not been reported.
Figure 10: The currently reported c.
2381T>C mutation (picture from Dr.
Jiao Bin's PPT) traced the source and further sequenced the patient’s father and mother to determine whether the patient’s mutation came from the father or the mother.
In the end, it was found that the patient's mutation came from the mother (Figure 11).
So the patient's mother was followed up.
The patient's mother is 54 years old and has a third-grade education level in elementary school.
His memory has declined for more than 10 years, his calculation ability has decreased slightly, and he can take care of himself in work and daily life.
I usually feel unhappy, worried and afraid, have been diagnosed with depression in the past, and have not taken medication regularly.
Neuropsychological assessment of the patient’s mother: MMSE (Mini-Mental State Examination): 18 points; MoCA (Montreal Cognitive Assessment): 11 points; AVLT (auditory verbal learning task, auditory Vocabulary Learning Test): 72 points.
The patient's mother has manifestations of cognitive decline.
The brain magnetic resonance of the patient's mother showed multiple white matter lesions.
Figure 11: Family verification (picture from Doctor Jiao Bin's PPT) There is currently no specific treatment for HDLS.
Because the CSF1R mutation affects the function of microglia, hematopoietic stem cell transplantation may have a therapeutic effect on the disease.
Symptomatic treatment includes: Parkinson's phenotype can try drugs such as levodopa, but the effect is not good; depression symptoms can try antidepressant drugs, but the long-term benefit is small; psychotic symptoms (aggressive behavior) can use antipsychotic drugs; Epilepsy medications should be started in any individual with seizures.
Summary: 1.
Neural Behcet is an exclusive diagnosis, especially when the treatment effect of hormones and immunosuppressants is poor, the diagnosis should be made with caution.
2.
There are many types of diseases related to white matter lesions, and comprehensive consideration should be given to clinical qualitative diagnosis.
3.
The clinical phenotype of HDLS patients is very heterogeneous, not only involving the central nervous system, but also involving multiple systems throughout the body.
4.
Inherited disease ≠ no cure, HDLS may be effective for bone marrow transplantation.
