Unresponsive don't just think of dementia

Central pontine myelinolysis (CPM) is a clinically rare metabolic demyelination disease

Author:Wang Lulu

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Case profile

Physical examination: T36.

Neurologic examination: clear consciousness, large isocircles such as bilateral pupils, about 2.

Admission diagnosis: (1) Causes of unresponsiveness and confusion to be investigated: central pontine myelinolysis (CPM)? (2) Electrolyte disorders: hyposodium, hypochloremia

Initial localization of qualitative diagnosis

Localization diagnosis: the patient is a middle-aged woman, with acute onset, mainly manifested as sudden retardation, confusion, with involuntary dancing of both upper limbs, localized in the

Qualitative considerations:

• CPM: patients have a history of severe hyposodium, sodium supplementation within 1 day to increase blood sodium by 26mmol/L, followed by sudden apathy and slow response, accompanied by involuntary dancing of both upper limbs, the disease should be considered, and further MR examination of the skull should be performed to confirm

• Hyponatremia encephalopathy: patients with significantly lower blood sodium levels before onset of the disease, so hyponatremia encephalopathy should be considered, which can be further corrected for electrolyte abnormalities and other causes can be excluded

• Hashimoto encephalopathy: patients have a history of hyperthyroidism, sudden change of consciousness, symptoms within 3 days, symptoms fluctuate, no bleeding focus on CT of the skull, normal CSF, the disease may be considered, and further thyroid function and thyroid antibody testing can be done to confirm

• Drug-induced psychiatric disorders: patients who have used antibiotics before onset (specifics unknown) need to consider the possibility of quinolones causing mental disorders, and further follow-up of medications is needed to clarify
.

Diagnosis and treatment

Post-admission check:

• Biochemical potassium 3.
10mmol/L, sodium 131mmol/L;

• FT3, FT4, sTSH, TPOAb, TGAb are normal
.

• Cerebrospinal fluid routine, biochemical, cytology, IgG index are normal
.

• Dynamic EEG shows mild abnormalities
.

• 4 days after the onset of the disease, no obvious abnormalities were seen on MRI of the skull; After admission, methylprednisolone was given 500 mg/day shock treatment, and the methylprednisolone
was gradually reduced after 5 days.

During the hospitalization, the patient gradually developed extrapyramidal symptoms such as limb stiffness and involuntary jitter of both upper limbs, and was treated with medopa, amantamantamine, baclofen, pilobedil (teshuda), clonazem, ethperisone, pramipexole to reduce muscle tone, dehydration and reduce cranial pressure, and symptomatic treatment of analgesia, and the increase in muscle tone lead ducts gradually improved
.

• 13 days after the onset of the disease, cranial MRI: patchy T1WI low signal, T2WI high signal shadow in the pontine, the realm is not clear, DWI is high signal, and no obvious enhancement is seen in enhanced scan; T2WI bilateral caudal nucleus, globus pallidus, and insula signals were increased, DWI showed slightly higher signals, and no significant enhancement
was seen in enhanced scans.

• 36 days after the onset of the disease, the cranial MRI: the pontine region saw a circular abnormal signal shadow, the side was not clear, the signal was low on T1WE, high signal on T2WE, high signal on DWI, and symmetrical T1WI low signal and T2WI high signal in the bilateral basal ganglion region of the other bilateral thalamus and bilateral basal ganglia were seen in the symmetrical low signal, T2WI high signal shadow, and slightly higher signal
on DWI.

• Discharge diagnosis: CPM; Electrolyte disorders: hypokalemia, hyposodium, hypochloremia
.

No abnormalities in MRI of the skull (4 days after admission)

Cranial MRI: bilateral caudal nucleus, globus pallidus, insula T1WI low signal [(A)], T2WI high signal shadow (B)]; DWI is seen with pontine patchy hypersignaling [(C)]; MRI enhancement scan without significant enhancement [(D)] (13 days after admission)

Cranial MRI: symmetrical T2WI hypersignal shadow in bilateral thalamic and bilateral basal ganglion regions [(A)]; The pontine region is characterized by a circular abnormal signal shadow with an unclear boundary, a high-signal shadow on T2W1 [(B)], a low-signal shadow on T1WI (C), and a high-signal [(D)] on DWI (36 days after admission).

Finalize qualitative diagnosis

Localization diagnosis: the patient is a middle-aged woman, with acute onset, mainly manifested as sudden retardation, confusion, accompanied by extrapyramidal symptoms such as limb stiffness and involuntary jitter of both upper limbs, and localization of the
brain.

Qualitative diagnosis:

• CPM: the patient has a history of severe hyposodium, normal sodium supplementation within 1 day, blood sodium rise of 26mmol/L, sudden apathy, slow response, accompanied by involuntary dancing of both upper limbs, the disease may be considered, although the fourth day of the onset of the skull MRI did not show the performance of pontine demyelination, but there are literature reports that the imaging changes of CPM can lag behind the clinical manifestations by 2 weeks
.

After that, the patient gradually developed involuntary mandibular jitter, bradykinesia, increased muscle tone and extrapyramidal manifestations, 13 days after the onset of the disease head MRI saw caudate nucleus, globus pallidus, insula T1WI low signal, T2WI is high signal, considering extrapontineal myelination (EPM), while DWI saw central symmetrical high signal foci of the ponchondron, consider CPM
.

36 days after the onset of the disease, cranial MR1 showed symmetrical abnormal signals in the pontons, bilateral caudal nucleus, globus pallidus, and island lobes, so CPM was considered to be more clear, and clinical classification considered to be coexisting
with the pontopontine appearance and the central pontine type.

• Hyponatremia encephalopathy: the patient's blood sodium level is obviously low before the onset of the disease, so it needs to be considered, but the psychiatric symptoms such as indifference after correction of hyponatalism after the correction of hyponatalism are still more aggravated than before, and the electrolyte abnormality alone cannot explain the progression of the disease, so it can be ruled out
.

• Hashimoto encephalopathy: patients have a history of hyperthyroidism, sudden change of consciousness, symptom relief within 3 days, symptoms fluctuating, no bleeding focus on CT of the skull, normal CSF, the disease may be considered, but thyroid function and TPO-AB, TGAB are normal, and Hashimoto encephalopathy is
not supported.

Causes and pathogenesis of CPM

At present, the etiology and pathogenesis of CPM are not clear
.

In early cases, most people with severe or chronic wasting disease, especially those with advanced alcoholism, are mostly associated with Wer-nicke encephalopathy, so its onset is thought to be related
to malnutrition.

Most scholars now consider the demyelination of nerves due to sharp changes in osmolality in the brain to be the main pathogenic mechanism, usually caused
by hyponatremia and correction of hyponatremia too quickly or excessively.

This view has been confirmed by Laureno et al.
through experiments, they repeatedly injected puerperitary posterior lobulin and abdominal water injection into dogs, so that dogs show a severe hyponatremia state, and then quickly correct hyposodium, thereby creating clinical and pathological changes
similar to human CPM-like.

Because the brain tissue is in a hypotonic state during hyponatremia, rapid supplementation of hypertonic saline can rapidly increase plasma osmolality, resulting in dehydration of brain tissue and blood.
The brain barrier is destroyed, and harmful substances pass through the blood-brain barrier to desheath the
myelin.

The literature reports that rapid correction of slow-forming hyponatremia is key to the occurrence of CPM, while rapid correction of hyponatremia that forms in the short term does not lead to CPM
.

Clinical features of CPM

(1) CPM is distributed and can occur
in both men and women at any age.

(2) CPM often occurs on the basis of severe primary diseases, limb laxative paralysis, chewing, swallowing and dysarthria, nystagmus, and eyeball coordination and movement disorder; May present with silence and complete or incomplete locked-in syndrome
.

(3) Sometimes it can be found in the thalamus, hypothalamus, striatum, inner capsule, deep cerebral cortex and similar white matter of the brain similar to pontine lesions, symmetrically distributed demyelination area, called extrapontine myelination (EPM).


The clinical manifestations of EPM are diverse, mainly characterized by symptoms
such as delayed dystonia, ataxia, or Parkinson's syndrome.

The pathological basis is the demyelination of nerve fibers in the striatum containing dopamine receptors, but are often masked by CPM pyramidal tracts and brainstem symptoms in the early stages, and are rarely apparent
.

(4) Some patients CPM manifestations can be masked by the coma of the primary disease, and when CPM pontine lesions are small, they can be completely asymptomatic and signless, so they can only be found and diagnosed
during MRI.

MRI performance characteristics of CPM

In the past, CPM required pathological certainty, but now it is basically clear with the help of MRI, mainly because the MRI manifestations of CPM have their own characteristics, including:

(1) CPM is symmetrical T1WI low signal and T2WI high signal shadow at the base of the ponbutus, Flair.
DWI is symmetrical high signal, and the central lesion of the pont is symmetrical in the axial position, sagittal position and coronal position, respectively, symmetrical triangle or butterfly, oval and bat wing changes, the sagittal position shows that the disease change is clear, the positioning is accurate, and the site and morphological characteristics of the lesion are the key to CPM diagnosis;

(2) No signs of occupancy;

(3) Enhanced scanning without obvious reinforcement;

(4) After treatment, the MRI lesions of the skull can be reduced and can also be completely restored, indicating that there is reversibility of demyelinating lesions;

(5) CPM lesions are symmetrical and do not conform to the circulation and distribution of blood vessels;

(6) EPM patients symmetrically involve bilateral basal ganglia, thalamus and subcerebellar cortex
.

Principles of treatment of CPM

At present, there is no specific treatment method for CPM, and it is still mainly supportive and symptomatic treatment, while actively treating the primary disease
.

Early high-dose hormone shock therapy may inhibit the progression of the disease, and other potentially effective treatments include plasmapheresis, intravenous immunoglobulin, neuronutrition, improved circulation, and hyperbaric oxygen therapy
.

Supplementation with various required vitamins and trace elements is also a necessary measure
.

In the acute phase, dehydrating agents such as mannitol and furosemide can be given to treat cerebral edema
.

Prevention of CPM

Since there is currently no specific treatment for CPM, it is particularly important
to prevent the occurrence of CM.

In order to prevent myelinlysis, electrolyte disturbances, especially hyponatremia, should be avoided as much as possible while actively treating the primary disease, and correct management of hyponatremia is the key to preventing the
occurrence of CPM.

However, the optimal treatment for hyponatremia has not been determined, and two points have been recognized: (1) correction of hyponatremia should be based on neurological symptoms rather than absolute values of serum sodium, and patients who are asymptomatic and neurologically unaffected should not infuse hypertonic fluids, regardless of blood sodium; (2) To slowly correct hyponatremia, the rate of correction of chronic hyponatremia can not exceed 0.
5 mmoL / L per hour, the increase in blood sodium in 24h generally does not exceed 10 mmol / L, and stop sodium supplementation when the blood sodium rises to 125-130mmoL / L
.