Craniectomy

In the past decades, the complexity of caring for patients with encephalitis has increased considerably. This is due, in part, to advanced diagnostic techniques such as the polymerase chain reaction (PCR) and the development of specific therapies for various viral infections. Most patients require critical care treatment during the acute stage of their disease because of seizures, fever, confusion, or increased intracranial pressure (ICP). Treatment and monitoring of raised ICP may be essential in those rare cases of encephalitis in which life-threatening edema develops. Barnett et al. ^[1] described ICP monitoring as a useful adjunct for therapy in severe encephalitis and as an indicator of further prognosis, since major elevations of ICP due to cerebral edema in encephalitis can cause further neurologic damage and even death from transtentorial herniation. Raised ICP in adult encephalitis, frequently encountered in herpes simplex encephalitis and other forms of encephalitis in adults, does require specific antiedematous treatment in up to three-fourths of patients. ^[2] According to Barnett et al., ^[1] aggressive management of raised ICP with signs of severe swelling on CT improves outcome in these patients. In their study the patients were treated with hyperventilation and administration of mannitol to reach an osmolality of more than 295 mOsm/l. However, even in their group five of ten patients died due to severe brain edema with resulting transtentorial herniation.

There have been recent proposals for decompressive surgery for control of otherwise intractable, elevated ICP for a variety of neurologic disorders such as head trauma, space-occupying hemispheric infarction, or subdural hematoma. ^[3-9] The surgical management of intracranial hypertension is directed at improving cerebral perfusion and preventing ischemic damage and mechanical compression of the brain against various intracranial structures such as the falx, tentorium, or the sphenoid ridge. However, especially in patients with cerebrovascular accidents, there is still controversy as to when and how to implement this invasive therapeutic procedure. ^[9]

Patients and methods.

We describe six patients with encephalitis of varying origin who developed severe brain edema in the clinical course and were treated with hemicraniectomy to control ICP. The technique for decompressive surgery has been described elsewhere: in brief, a large bone flap including the frontal, parietal, temporal, and parts of the occipital squama was removed so that the floor of the middle cerebral fossa could be explored. The dura was fixed at the edge of the craniotomy to prevent epidural bleeding. The dura was then opened, and an adjusted, biconvex dural patch, made of lyophilized cadaver dura or homologous temporal fascia, was placed into the incision. The size of the dural patch was usually 15 to 20 cm in length and 2.5 to 3.5 cm in width. An artificial bone flap was implanted 6 to 12 weeks after operation.

Case reports.

Patient 1.

A 32-year-old woman developed an influenzalike respiratory illness with headache, fever up to 38.8 degrees C, and cough. Within 3 days after symptom onset she developed a moderate, right-sided hemiparesis. She was admitted to a primary care center where her clinical condition deteriorated. She became stuporous and had to be intubated and artificially ventilated. At that time she was treated with osmotherapy and mild hyperventilation. CT at that time revealed left-sided, pronounced white matter edema; the CSF was investigated and showed 400 white blood cells/dl, glucose of 48 mg/dl, and protein 70 mg/dl. Serologic findings for bacterial, viral, and fungal agents were all negative. PCR for herpes simplex virus DNA and tuberculosis were both negative. For further brain edema therapy the patient was transferred to our neurocritical care unit (NCCU). On admission she had a left-sided, dilated, and fixed pupil: on noxious stimuli, she showed extensor posturing. For ICP control a large, left-sided craniectomy was performed and an epidural ICP probe was inserted ipsilateral to the craniectomy, 3 days after symptom onset. Maximum ICP in the clinical course was 45 mm Hg. CSF evaluation 3 days later showed 0 red blood cells and 1 white blood cell and a protein content of 60 mg/dl. In serum, cold agglutinins could be detected, with a positive Coombs' test. The antibody titer at 4 degrees C was 1:320 and rose up to 1:64. The red blood cell morphology was normal and no spherocytes were visible. The patient had no signs of hemolysis. The PCR for Mycoplasma pneumoniae at that time was negative. No titer changes indicative of either rubella or infectious mononucleosis could be detected. In the further clinical course ICP values up to 40 mm Hg were measured. For antiedematous therapy mannitol, thiopental, and THAM buffer were administered. The electrophysiologic examinations revealed normal brainstem auditory-evoked potentials (BAEP), and somatosensory-evoked potentials (SEP) showed increased interpeak latency (IPL) N13 through N20 and a bilaterally decreased N20/P25 amplitude. On MRI bilateral left-sided marked white matter edema was visible, in addition, bilateral hemorrhagic lesions of the occipital lobe were detected (Figure 1). At that time the patient was still comatose and showed bilateral extensor posturing on painful stimuli. After 4 weeks of artificial ventilation, still in a comatose state, she was transferred to a rehabilitation clinic. Nine months later the only neurologic deficit was a severe impairment of short-term memory; otherwise she had recovered completely.

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Figure 1. (Patient 1). Noncontrast CT at upper level of basal ganglia (A) and brainstem (B) level performed after clinically observed deterioration shows left-sided white matter edema with effacement of the cerebral sulci. At this time the patient became stuporous and needed mechanical ventilation. Note severe midline shift. Contrast-enhanced CT (not shown) failed to demonstrate abnormal enhancement. Decompressive surgery was performed on the same day. (C) After decompressive surgery CT showed only a small area of parenchymal hypodensity in the left hemisphere, without midline shift.

Patient 2.

A 29-year-old woman complained of "flulike" symptoms. She experienced a gradual onset of myalgias, arthralgias, body temperatures of up to 38.7 degrees C, and a sore throat. She was first seen in another hospital because of severe headache and vomiting. Within hours she developed a severe, right-sided hemiparesis with aphasia and impairment of consciousness. CSF study revealed 200 white blood cells and a protein content of 160 mg/dl. Serologic findings for bacterial, viral, and fungal agents were negative. When she was transferred to our NCCU, 3 days after onset of symptoms, she had a unilaterally dilated and fixed pupil for almost 6 hours, despite extensive osmotherapy with mannitol (1 g/kg every 3 hours). On admission neither pupil reacted to light. On noxious stimuli, she showed extensor posturing. The motor signs were positive on the left side. CT at that time showed severe, left-sided brain edema with compressed basal cisterns and midline shift (Figure 2). A large, left-sided hemicraniectomy was performed to control ICP and an epidural ICP probe was inserted ipsilateral to the craniectomy, with a maximum ICP of 40 mm Hg. Spinal tap 7 days after neurosurgery showed 2 white blood cells, glucose of 110 mg/dl, and a protein content of 30 mg/dl. In the clinical course, results of Coombs' test were positive, with a cold agglutinin titer of 1:64 at 4 degrees C. In the complement fixation test the titer for M pneumoniae rose from 1:16 to 1:64, while PCR for M pneumoniae was negative both in serum and CSF. The electrophysiologic examinations showed bilaterally increased IPL in the BAEP, and in the SEP increased IPL N13 through N20 and a bilaterally decreased N20/P25 amplitude. MRI visualized bilateral white matter edema. One month later the patient was already able to communicate and again 6 months after that she was able to be discharged from a rehabilitation center with only a mild hemiparesis of the right side and no signs of aphasia.

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Figure 2. (Patient 2). (A) Presurgical noncontrast CT shows a severe left-sided brain edema with effacement of left-sided cerebral sulci and marked shift of midline structures to right. (B) Note the bilateral compressed and nonvisualized basal cisterns and beginning of disturbance of the cerebrospinal fluid circulation. At this time the patient showed areactive pupils and no response on painful stimuli. Contrast-enhanced CT (not shown) failed to demonstrate abnormal enhancement. Decompressive surgery was performed on the same day. (C) CT after large left-sided hemicraniectomy shows herniation of brain through the bone defect but no midline shift.

Patient 3.

This 39-year-old man complained 6 days before admission of headache, fever up to 39 degrees C, myalgias, and night sweats. He then suddenly developed a severe, right-sided hemiparesis with aphasia. Because of severe impairment of consciousness he had to be intubated and ventilated. He was then treated with osmotherapy and mild hyperventilation. On admission to the NCCU the patient was sedated; the corneal reflex was absent on the right side, and pupil size and response to light were symmetric. No reaction could be elicited on painful stimuli. CT on admission revealed left-sided white matter edema with midline shift and compression of the third ventricle (Figure 3). Hemicraniectomy was performed 3 hours after admission to the NCCU. A brain biopsy at that time conclusively diagnosed an inflammatory process. CSF examination 5 days later revealed 0 white blood cells, glucose of 52 mg/dl, and a protein content of 240 mg/dl. Serologic findings for bacterial, viral, and fungal agents were negative. The Coombs' test was positive and the cold agglutinins were positive with a titer of 1:32. In the further clinical course the cold agglutinin titer decreased to 1:4. PCR examination for DNA of M pneumoniae and herpes simplex virus was negative. The complement fixation test for M pneumoniae was negative as well. Electrophysiologic examinations showed bilaterally normal BAEP, and SEP had increased IPL N13 through N20 and a left-hemispheric decreased N20/P25 amplitude. The patient recovered completely with no further neurologic deficit.

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Figure 3. (Patient 3). (A) CT shows severe left-sided brain edema, compression of left lateral and third ventricle, midline shift to right, and effacement of left-sided cerebral sulci. (B) The basal cisterns are bilateral compressed. Note the beginning of disturbance of the CSF circulation before decompressive surgery. (C) Postoperative CT shows herniation of brain through the bone defect and regression of mass effect. Contrast-enhanced CT (not shown) failed to demonstrate ill-defining patchy or gyriform enhancement, suggestive of encephalitis.

Patient 6.

A 45-year-old woman was admitted to our department because of dizziness and slight fever of 38.3 degrees C. Within 24 hours she developed a severe right-sided hemiparesis, conjugated gaze palsy, global aphasia, and coma. She was admitted to the intensive care unit for intubation and artificial ventilation. CT at admission showed a white matter hypodensity of the left hemisphere with effacement of the sulci but no midline shift or compression of the basal cisterns. Subsequent control CT showed a massive space-occupying hypodensity in the left hemisphere (Figure 4). Selective digital subtraction angiography of the internal carotid and vertebral arteries revealed signs of a massive parietal space-occupying lesion but no vascular malformation, vasculitis, or large-vessel disease. Lumbar puncture yielded normal CSF with a protein level of 140 mg/dl, normal cell count, glucose, IgG index, and no oligoclonal bands. Bacterial, fungal, viral, and tuberculosis test results were negative. Blood parameters of vasculitis such as antistreptolysin, antibodies against double-strand DNA, antinuclear factors, extractable nuclear factors, mitochondrial antibodies, complement, and immunofixation electrophoresis were normal. Brain biopsy demonstrated satellitosis and scarce perivas cular mononuclear cells. Apart from these rather unspecific findings, no clear evidence for a specific pathologic process, e.g., inflammation or tumor, was obtained. Further diagnostic procedures such as biopsies of muscle, nerve, and skin did not demonstrate pathologic findings. Since conservative antiedematous treatment with steroids, hyperventilation, osmodiuretics, and barbiturates was unsuccessful, decompressive craniectomy was performed 6 days after admission. Subsequent CT control examinations showed a slow reduction of the white matter edema. The patient was extubated 14 days later. Subsequently she recovered completely and retained no focal neurologic deficit. For intermittent focal seizures she was treated with carbamazepine. However, following CT examination 8 months after admission still showed white matter edema on the left side.

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Figure 4. (Patient 6). (A) Compression of left lateral ventricle with no focal parenchymal hypodensity. (B) After craniectomy, severe edema of left frontal and temporal white matter also involving left thalamus. There is right-sided shift of midline structures. (C) After covering craniotomy by palacos, further enlargement of ventricles, but no edema.

Discussion.

Contemporary virologic methods frequently allow rapid and specific identification of viruses or other pathogens, but the etiology remains uncertain in 25% or more of encephalitis patients. ^[10] Although acyclovir substantially reduces mortality and improves outcome in patients with herpes simplex encephalitis, supportive care is the only therapy available for most other patients with encephalitis. ^[2,11] In our group the infectious agent could only be recognized in patients 4 (M pneumoniae) and 5 (herpes simplex). However, serologic findings also suggested M pneumoniae infection in patients 1 to 3. Patients 1 through 4 all showed a similar constellation of positive direct Coombs' test with the detection of cold agglutinins. These IgM class antibodies directed toward the I antigen of erythrocyte membranes usually develop during the first 10 days of illness. These findings, together with the history of "flulike" symptoms, are often encountered in Mycoplasma infection; however, transient cold agglutinins are also found in infectious mononucleosis and other viral infections such as rubella, HIV, and adenovirus pneumonias. Typically, these patients have no significant hemolysis, and spherocytes are rarely seen. ^[12] Clinically it is not unusual to encounter patients with suspected mycoplasmal infection in which the diagnosis remains uncertain, particularly in those outside of the lung. ^[13] Neurologic disease associated with M pneumoniae is well recognized; most reports describe encephalitis, meningoencephalitis, or psychosis and transverse myelitis. ^[14,15] CNS manifestations appear in one of 1,000 patients with M pneumoniae-associated infections. Encephalitis is the most frequent manifestation. The onset is usually acute, with depressed consciousness, convulsions, pareses, and other neurologic signs. Severe disease and even fatal outcome are known in this complication. ^[16,17] Several authors described the course of M pneumoniae encephalitis. ^[14,16,18] The risk of death or severe damage seems markedly increased-at least in children-in patients with herpes simplex encephalitis or Mycoplasma encephalitis. ^[19] In our patients brain edema was the main complication of infectious encephalitis.

Serial evoked potentials in these patients were similar to the findings of Krieger et al., ^[20] in that evoked potentials indicate raised ICP in supratentorial mass lesions, but do not predict sequelae. Krieger et al. ^[20] could demonstrate that BAEP serve as a valuable prognostic predictor, once effective therapy is instituted.

For early and probably most effective treatment of severe, space-occupying encephalitis the "malignant" character of the brain edema has to be recognized early after the onset of symptoms. Clinical factors such as coma, pupillary nonreactivity, and dense hemiplegia are not really early indicators, but rather the signs of a developing severe brain edema. Integration of the clinical examination with early CT findings and new imaging techniques, such as perfusion and diffusion weighted MRI, might permit determination of the clinical significance of brain edema-similar to ischemic stroke-early after onset, thereby allowing us to gauge aggressive treatment forms such as decompressive craniectomy, before life-threatening brain swelling and herniation occur. ^[21,22]

Little data about the effectiveness of decompressive craniectomy in severe encephalitis are available. Jourdan et al. ^[23] reported a patient with presumptive encephalitis in whom ICP could not be controlled by medical treatment. By performing decompressive hemicraniectomy this patient recovered with no disability.

Although this is a small anecdotal series, hemicraniectomy with dural augmentation appears to be a lifesaving method for the therapy of severe brain edema following encephalitis. The value of conventional therapies of raised ICP, consisting in artificial ventilation, osmotherapy, and barbiturate administration, is disputable. ^[24-26] For a long time, chronic hyperventilation with a target pCO₂ of 25 to 30 mm Hg was considered an effective strategy for temporarily decreasing ICP after intubation and initiation of mechanical ventilation. Recently, vigorous chronic hyperventilation was discouraged since it may reduce the brain's ability to tolerate ischemia and therefore be more harmful than beneficial. ^[24] The use of osmotherapeutics such as glycerol or mannitol may actually hasten tissue shifts due to compartment ligation and aggravation of brain edema. ^[27] Barbiturate therapy has of yet failed to prove to be of any benefit in the treatment of edema after severe brain injury. ^[25] Moreover, a number of studies have shown severe side effects of high-dose barbiturate therapy, consisting of severe and prolonged arterial hypotension, cardiovascular complications, and severe infections. ^[25,28] The value of decompressive surgery to control increased ICP in cerebral ischemia or head trauma has been described by several authors. ^[9] Frank ^[26] concluded that the good outcome from surgical decompression in patients with large hemispheric infarction provides greater benefit than medical treatment modalities aimed to lower ICP, which are, until now, poorly founded. Unlike cerebral ischemia, in severe encephalitis the initial neurologic deficit seems to have no impact on long-term clinical outcome after decompressive surgery, since all of our six patients recovered with no disability.

We conclude that the outcome in our patients after decompressive surgery, even though they all had signs of unilateral uncal herniation, support surgical decompression as a therapeutic option in patients whose condition deteriorates while receiving medical therapy for increased ICP.