Ischemia of corpus callosum

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

Dear Editor,

we present a rare case of corpus callosum ischemia (CC). The CC is the largest white matter structure of the brain and is the main commissural pathway connecting the two cerebral hemispheres, consisting of 200-250 million contralateral axonal processes [1]. The blood supply to the CC is provided mainly from the carotid basin (mainly via the arteria cerebri anterior [ACA] and additionally from the arteria communicans anterior [ACoA]), and partly from the vertebrobasilar basin [2,3]. The rostrum and genu are supplied by the subcaudal and medial callosal arteries arising from the ACoA. Four branches arise from the pericallosal artery (a continuation of the ACA) and provide most of the supply to the CC body. The posterior pericallosal artery, a branch of the arteria cerebri posterior (ACP), is a short penetrating arteriole supplying the splenium. There are anastomoses between the callosal branches of the ACA and ACP near the tip of the splenium. Thus, an isolated occlusion supplying branches from the ACA or ACP watershed does not necessarily lead to interruption of blood supply and subsequent infarction. Given this, CC ischemias are relatively rare [4].

A seventy-three-year-old patient, premorbid with no neurological deficit, was admitted for a week of persistent rotational vertigo and spatial uncertainty. Personal history was followed for paroxysmal atrial fibrillation (on chronic rivaroxaban), arterial hypertension, dyslipidemia, and type 2 diabetes mellitus. At the age of 40, he underwent percutaneous coronary intervention after myocardial infarction. Objective neurological findings on admission included mild asthasia and abasia, and he was stable ventilatory and circulatory, afebrile. Laboratory findings were only leukocytosis (12.4×10⁹/l) with mild elevation of CRP (13.4 mg/l). Native CT of the brain showed minor hypodensity in the CC plexus (Figure 1A). Ultrasonographic examination verified minimal atherosclerotic changes in the carotids and possible hypoplasia a vertebralis on the right. Initial EEG examination was normal with normal findings. After 5 days of admission, there was a progression of impaired consciousness to grade IV somnolence (with fluctuation during the day between grade II-IV), CAM-ICU repeatedly negative. Furthermore, moderate dysarthria, mixed fatal disorder and mild right-sided hemiparesis developed. Follow-up laboratory examination did not explain the deterioration of consciousness. On follow-up brain CT, progression of hypodensity in CC, without postcontrast saturation (Figure 1B). The control EEG graph described nonspecific abnormal encephalopathic findings with a slightly diffusely slowed and disorganized background. Because of the high risk of blood hypodensity in CC, rivaroxaban was discontinued and low molecular weight heparin (as a prophylaxis for thromboembolic disease) and acetylsalicylic acid were added to the medication. Liquidological examination verified mild hyperproteinorachia (986 mg/l) without pathological pleocytosis, while qualitative cytological examination of the lysate was normal. There was positivity of IgG antibodies against tick-borne meningoencephalitis in serum and liquor and positivity of IgG antibodies against Borrelia burgdorferi in serum (negative in liquor). Testing for autoimmune encephalitis-specific antibodies including paraneoplastic antibodies was negative in serum and liquor. A PCR panel of meningitides (Herpes simplex virus 1,2, Varicella zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes virus 6-7) was also negative. MRI of the brain, performed on day 10 of hospitalization, showed extensive CC involvement without evidence of postcontrast saturation, most likely in acute ischemia (Figure 2). In the differential diagnosis, cytotoxic CC lesions (CLOCC), primary lymphoma or glioblastoma multiforme were considered. Later in the course of hospitalization, tracheobronchitis developed with dyspnea and the need for oxygen therapy, with a laboratory elevation of CRP 83.4 mg/l and leukocytosis 24×10⁹/l. Antibiotic therapy with sulfamethoxazole/trimethoprim was empirically instituted. Chest X-ray examination revealed no inflammatory changes. Despite the therapy instituted, progression of respiratory insufficiency occurred in the context of upper airway obstruction with deepening of impairment of consciousness into snoring. On the fourteenth day of hospitalization, orotracheal intubation (OTI) was required and invasive ventilation was instituted, and analgosedation with propofol and sufentanil was initiated. Empirical escalation of antibiotic therapy to piperacillin/tazobactam was performed. After treatment of the respiratory infection and normalization of ventilatory parameters, an attempt was made to wean the patient, but after weaning, coma-level impairment of consciousness (Glasgow Coma Scale 3) persisted with symmetric preservation of both trunk and diencephalic reflexes. Native CT of the brain 5 days after OTI placement showed fresh hypodensities in the basal ganglia and especially in the white matter periventricularly, more to the left (Figure 1C, D). EEG showed a nonspecific moderately abnormal recording (baseline activity labile in the alpha and beta bands, diffusely admixed with nonspecific theta waves), with no epileptiform abnormality. A targeted biopsy was performed 8 days after OTI insertion with the finding of an edematous white matter with no conclusive evidence of tumor infiltration. Subsequent findings were compatible with a diagnosis of ischemic lesion/necrosis of the CC. Despite maximal support of organ functions and discontinuation of analgosedation (analgosedation discontinued for 8 days), there was no improvement in the state of consciousness and the patient remained in deep coma. Due to the extremely unfavorable prognosis, comfort care was initiated for the patient. The following day, uneventful exitus lethalis occurred.

The clinical manifestations of acute CC infarction are poorly specific and varied, as they often merge with cerebral infarction in another localization. Yang LL et al [5] describe cognitive and fatal disturbances, uncertainty in action and forced laughter or crying; only in 4% of cases the so-called alien hand syndrome was present. In our patient, instability, speech impairment and mild hemiparesis were present at baseline. Among the most common risk factors, arterial hypertension, diabetes mellitus, nicotinism, atherosclerotic changes in the carotid arteries, hyperlipidaemia, obesity, history of cerebral infarction and ischaemic heart disease were listed [5]. Vascular risk factors were also present in our patient.

CC infarcts may exhibit varying degrees of expansive behavior, which is commonly seen in malignant cerebral infarction, but other etiologies such as tumors -⁠ glioblastoma multiforme [6], gliomas and lymphomas [7] -⁠ are often considered in CCs where CMP is not considered. Approximately 25% of glioblastomas show CC infiltration at diagnosis, which is associated with a poor prognosis [8]. CLOCC must also be considered -⁠ this has been found in association with drug therapy (some antiepileptic drugs or antibiotics), malignancy, infection (often viral), subarachnoid haemorrhage, metabolic disorders, trauma (diffuse axonal injury), autoimmune diseases (multiple sclerosis, systemic lupus erythematosus), epileptic seizures and other causes [9]. Symptoms of CLOCC can be mild but also very severe. CLOCC are often, but not always, reversible. MRI plays a key role in the diagnosis of CLOCC, with typical findings of lesions hyperintense in T2 weighted images, fluid attenuated inversion recovery (FLAIR) sequences and diffusion weighted imaging [DWI], and hypointense in T1 weighted images and apparent diffusion coefficient (ADC) maps [10]. In the differential diagnosis of structural CC lesions, cases of Marchiafava-Bignami disease, a rare disorder specifically manifested by demyelination/necrosis of the CC and nearby subcortical white matter, typically in poorly nourished alcoholics with B vitamin deficiency, have also been described. Also in the case of our patient, CLOCC, primary lymphoma or glioblastoma multiforme were considered in the differential diagnosis.

In conclusion, although CC ischemia is rare, it should be thought of in the differential diagnosis when it is involved.

Financial support

R. Herzig and V. Weiss were supported by Charles University (Cooperatio program, NEUR scientific area). R. Herzig was supported by the Ministry of Health of the Czech Republic -⁠ RVO (FNHK, 00179906).

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.