Results

Preoperative survey data

ES were observed in 45 patients with insular tumor (88.2%). Five patients had general cerebral and focal symptoms. In one patient, tumor was detected after examination for panic attacks and agoraphobia.

Generalized convulsive seizures without aura were observed in 8 patients (5 patients with left-sided tumor, 3 patients with right-sided tumor). These patients had the largest tumor. The neoplasm more significantly spread to adjacent medial parts of temporal and frontal lobes compared with other tumors. Other 6 patients had secondary generalization of convulsive activity with development of general convulsive attacks of different incidence after aura. Complex focal seizers were diagnosed in 4 patients (focal paroxysmal manifestations with various degrees of consciousness impairment and no generalized seizures). In total, various degrees consciousness impairment were observed in 18 (35.2%) patients. Visible focal component of convulsive attacks was absent in only 8 patients.

Multicomponent focal seizures were diagnosed in 41 cases. Vegetative manifestations combined with olfactory and gustatory hallucinations were the most common.

Incidence of olfactory and gustatory hallucinations was similar in patients with different lateralization of insular tumor (26 out of 51 (51%) patients). Left-sided neoplasm was followed by isolated olfactory hallucinations in 2 patients, olfactory and gustatory hallucinations in 3 patients, olfactory disorders in 4 cases and isolated gustatory hallucinations in 4 patients (n=13).

Right-sided insular tumor resulted olfactory hallucinations in 5 patients, combination of olfactory and gustatory hallucinations in 3 patients, isolated gustatory hallucinations in 4 patients (n=12).

Qualitative analysis of olfactory and gustatory hallucinations was of great interest. Hallucinations were presented by unpleasant smell and taste in all patients regardless the side of the tumor. Sometimes these hallucinations were very harsh and painfully-obsessive. Sensations of smell and taste, as well as the entire structure of the focal component, were always the same in certain patient. Patients often felt the smell of burning, “something burned” (for example, smell of burned rubber), gas, sulfur, something sharp, “nasty”, chemical, “something that cannot be in nature, perverted smell some kind". It could be very sharp chemical smell of coconut, some kind of complex chemistry, camphor or ether, or something very sour, inedible. Thus, there was always smell of something dangerous that should be avoided. If the smell was characterized by at least some natural shade, for example, gas, burning, patients did not always realize the painful nature of this smell. They tried to find its source with involvement of relatives and noted sudden appearance and fast disappearance of the smell. Some patients with different lateralization of tumor had hyperesthesia of smell. These disorders periodically resulted perverted perception of well-known smells (olfactory illusions). For example, 2 patients felt sudden smell of chemistry or unusual odor from well-known food. These sensations were very sharp and unusual. Therefore, patients later refused to eat the same food because they afraid to fell this smell again. Another patient was very surprised by her suddenly sharpened smelling (“for example, I feel bread in the kitchen even if the table is closed”). In other 2 patients, the same real sharp external smell could cause a focal seizure like a reflex epilepsy. For example, very peculiar seizures of reflex epilepsy were noted in a patient with right-sided insular tumor. In that case, a sharp smell of citrus fruits was followed very unpleasant metallic taste in the mouth and short-term weakness in the left limbs. In another patient, real pungent smell of "burnt diesel fuel" (patient worked as a truck driver) resulted feeling "that loss of consciousness will occur soon, something is being changed".

The variety of gustatory hallucinations included in the structure of partial seizures in patients with insular tumors was small and did not depend on tumor lateralization. These hallucinations were always very unpleasant and usually manifested by sharp sensation of something sour, nauseous, chemical and metallic, always inedible, dangerous. One patient said that "the taste of sour was so strong and nauseous that I immediately wanted to rinse my mouth". Sensation of sour or chemical taste could be combined with the same simultaneous sensation of smell and nausea with hypersalivation. Patients said that "mouth and nose are filled with these sensations, it is difficult to say where feeling are stronger". However, sudden nausea with hypersalivation lasting 1—2 minutes on the background of clear consciousness were not associated with olfactory and gustatory hallucinations in two patients. Nausea arose suddenly and was not accompanied by unpleasant sensations in the stomach.

We do not exclude that incidence of olfactory and gustatory hallucinations could be higher in patients with insular tumors, since not all patients with olfactory and gustatory hallucinations associated these disorders with brain disease. For example, one patient briefly and suddenly felt the smell of gas even in inappropriate places. However, she continued to search for source of this smell and confidently involved her relatives into this process. She reported this disorder only after comprehensive survey. Another patient with left-sided insular glioblastoma has been unsuccessfully examined for several months by various gastroenterologists for sudden severe nausea and sour taste in the mouth on the background of clear consciousness. There were only complaints of paresthesia in the right limbs at admission. Clear clinical diagnosis was determined only during neuropsychological examination. Paroxysm of severe nausea and sensation of sour taste in the mouth occurred during this survey. Therefore, patients with these tumors need for targeted detailed questioning.

Another common component of focal seizures in patients with insular tumors was sudden unmotivated emotions of fear, anxiety or panic (n=9, 17.6%). None of the patients had positive affective paroxysmal component. Affects of anger or rage were absent too. The affective component was a part of focal seizures in 3 patients with left-sided insular tumor and 6 patients with right-sided tumor. Anxiety and fear were necessarily accompanied by vegetative manifestations. For example, one patient with left-sided tumor woke up several times a night due to a strong unmotivated fear accompanied by vegetative manifestations (severe palpitations, sweating, severe nausea). As a result, this patient was afraid to go to bed and fall asleep. Correct diagnosis and administration of anticonvulsants were followed by regression of these disorders.

It should be noted that partial spread of tumor to the mediobasal parts of the temporal lobe and less often basal parts of the frontal lobe was observed in all patients with seizures of anxiety and fear.

Focal components of seizures included vegetative manifestations in 27 (53%) patients with insular tumors. These disorders were similar and did not depend on tumor lateralization: feeling of giddiness, rising “wave” from below (the so-called “ascending epileptic sensation”), sweating, palpitations, feeling of heat, cold, redness of face, epigastric discomfort, nausea, hypersalivation, less often shortness of breath. Vegetative manifestations could be combined with other components of seizures - fear, olfactory or gustatory hallucinations. However, vegetative disorders could be independent symptoms too. In some patients, these autonomic paroxysmal disorders were combined with automotor component (gestural automatisms, swallowing, and other symptoms of oral hyperkinesis). Some patients with tumor spread to the temporal lobe had seizures by deja vu type, derealization (two patients with right-sided tumor) or complex acoustic hallucinations (“the same male voice” - one patient with left-sided tumor). All these symptoms are considered to be characteristic for medial temporal epilepsy 11—13 and could indicate spread of epileptic activation in limbic structures.

In 12 patients, seizures included numbness, clonic convulsions or short-term weakness in contralateral extremities. Sometimes these disturbances were associated with slurring speech and autonomic disorders. These signs were observed in patients with tumor of posterior parts of the insula and spread to the frontal and/or parietal lobes.

We analyzed epileptic seizures in 50 patients with isolated temporal tumors and 50 patients with frontal lobe tumors to clarify paroxysmal symptoms of insular tumors (Table).

Medio-basal localization of temporal lobe tumors prevailed. Syndromes of temporal lobe epilepsy are well understood. There are amygdalo-hippocampal (medial or mesial) and lateral temporal lobe epilepsy [11—13]. In case of advanced lesions, seizures could be characterized by the symptoms typical for both temporal epilepsies.

The first thing that attracted attention in comparison of seizures in patients with temporal and insular tumors was higher percentage of seizures with certain form of consciousness impairment in patients with temporal tumors. Changes of consciousness occurred in 42 (84%) out of 50 patients. These could be twilight states, non-convulsive equivalents, secondary generalization with general convulsive attacks after various auras and general convulsive attacks without previous auras.

Olfactory and gustatory hallucinations were also observed in patients with temporal tumors (n=8, 16%). Five of these patients had focal component of seizures in the form of an unpleasant (chemical) smell (2 patients with right temporal tumor and 3 patients with left temporal lobe). Another 2 patients with left-sided neoplasms suffered paroxysmal swelling of unpleasant taste (acetone). One patient with right-sided tumor had simultaneous sensation of unpleasant odor and taste.

Thus, taste and smell were unpleasant, chemical and unnatural as in patients with insula tumor. However, incidence of olfactory and gustatory hallucinations in patients with temporal tumors was significantly lower than in patients with insular tumors (16% vs. 51%). It should be emphasized that tumor was large in all 8 patients and occupied anterior areas of the temporal lobe (pole) or it was widespread, medio-basal, with involvement of anterior parts of the temporal lobe.

Another focal component with similar qualitative features observed in patients with insular tumors was affective aspect. Affect was always represented by strong sudden unmotivated fear, anxiety or sometimes panic in patients with both temporal and insular neoplasms. There was no anger or any positive emotions. Fear and anxiety were accompanied by tachycardia, sometimes reddening of the face, sweating. Thus, vegetative manifestations were very similar to natural reaction of intense fear. Feeling of fear was noted in 6 patients with right-sided temporal tumor and only in 1 patient with left-sided neoplasm (only 14% of patients). Medial and more often anteromedial spread of the tumor to the temporal lobe was observed in all patients. It is important to note that attacks of fear were more common in patients with right-sided temporal or insular tumors.

Focal autonomic components of seizures were noted in only 19 (38%) patients with temporal tumors and almost exclusively predominant medio-basal localization. Incidence of these disorders did not depend on tumor lateralization. Contrary to expectations, autonomic manifestations of seizures were not so pronounced and multicomponent in patients with temporal lobe tumors as in those with insular neoplasms. In most cases, one or two vegetative symptoms occurred prior to loss of consciousness. Short aura was followed by quick impairment of consciousness in most patients with temporal tumors.

The data of 50 patients with frontal lobe tumors were analyzed (Table 1). Seizures were observed in 48 (96%) of these patients, general seizures (sometimes in combination with focal seizures) or secondary generalization of focal seizures – in 39 (81%) patients. General convulsive attacks occurred in patients with different localizations of tumor. However, seizures were more common in the cases of tumors of left premotor area (17 out of 48 patients), especially in patients with deep or medial spread of the neoplasm. Other authors also pointed to the left premotor zone as the most epileptogenic area 14. Small cortical tumors in 8 patients resulted simple partial seizures in accordance with functional area of the frontal cortex. Focal components similar to the temporal ones preceded secondary generalization of seizures in 2 patients with tumors of the right opercular area: “ascending wave” with unpleasant sensations in the upper half of the body, gestural automatisms. This similarity with temporal seizures could be explained by anatomical spread of the tumor in the depth of Sylvian fissure or propagation of epileptic activity on the medial parts of the temporal lobe.

Very interesting diagnostic data were obtained in 3 patients with mediobasal tumors followed by infiltration of the frontal lobes near the olfactory nerves, tracts and anterior perforated substance. Some fibers from the olfactory bulb finished in olfactory tubercle near anterior perforated substance. None of these patients had olfactory hallucinations. However, one patient with right-sided tumor noted olfactory hyperesthesia with severe faintness in response to pungent odors. These complaints required examination of patient and brain tumor was diagnosed.

According to neuropsychological survey data, only 7 patients with insular tumor had almost no cognitive impairment. It should be emphasized that right-sided neoplasm was found in 5 of these patients. Two patients with left-sided tumors were teachers with well-developed speech that possibly contributed to compensation of mild impairment of auditory-speech memory. Gr II glioma was diagnosed in 6 patients without clear cognitive impairment, glioma Gr III — only in 1 patient. There were only focal ES in all these patients (unpleasant taste in the mouth, burning smell, cramps in the left extremities).

Disorders of higher mental functions were detected in 41 (80%) patients. Memory disorders were the most common and diagnosed in all these patients. However, features and severity of cognitive impairment significantly depended on the side and spread of the tumor process.

Seven patients with left-sided tumor had elements of different aphasia at admission confirming partial spread of the tumor (and/or peritumorous edema) to the frontal or temporal lobe (efferent motor or acoustic-mnestic). Glioblastoma Gr IV was diagnosed in 5 out of 7 patients with aphasia, astrocytoma Gr III — in 2 patients. Thus, high grade gliomas resulted clear preoperative focal symptoms (aphasia in these cases).

In other 26 patients with left-sided tumor, memory impairment was predominant and diagnosed only after neuropsychological examination. Korsakovsky syndrome was not detected. All patients were correctly oriented and rarely complained of memory impairment at the household level. Neuropsychological survey revealed modally nonspecific memory impairments (i.e. there were both auditory-speech and visual disturbances). However, auditory-speech memory disorders clearly prevailed and were severe in some patients. Delayed reproduction of words after presentation of interference was predominantly disturbed (serial count, holidays listing).

However, delayed reproduction of words was supplemented by introduction of extraneous inclusions in some patients (impaired selectivity of traces). These findings confirmed the role of dysfunction of the basal-medial parts of the frontal lobes in memory impairment. As a rule, patients reproduced meaningful material much better (story-fable) compared with random words. Visual memory impairment (narrowing of the volume) was diagnosed during direct reproduction of the figures.

Severity of preoperative mnestic disorders was various in different patients. As a rule, worse disturbances were observed in patients with tumors Gr III and IV and in those with significant spread of the tumor to mediobasal parts of the frontal and temporal lobes. In most patients, preoperative memory impairment was supplemented by the symptoms from adjacent cerebral areas (especially from the frontal lobe). For example, these were motor and intellectual inertness, impaired dynamic praxis and reciprocal coordination, perseveration (in motor sphere as a rule).

In 10 patients with right-sided tumor, preoperative memory disorders also prevailed (predominantly auditory-speech sphere). However, these disorders were not so pronounced as in patients with left-sided neoplasm. Predominant impairment of auditory-speech memory in case of right-sided tumor indicated mnestic disorders due to dysfunction of the deep parts of the brain (mediobasal parts of temporal and frontal lobes) rather cortical segments. Qualitative features of memory impairment were similar to those associated with left-sided insular tumors. Some patients with right-sided tumor were characterized by reduced criticism of their condition and emotional disinhibition prior to surgery that also confirmed functional involvement of adjacent mediobasal parts of the right frontal lobe.

Postoperative survey results

In postoperative period, patients received anticonvulsant therapy and ES were absent within the follow-up period.

Features and severity of neuropsychological symptoms clearly depended on the side of surgery, presence or absence of intraoperative complications and tumor spread to adjacent brain parts. There were several groups of patients depending on features of neuropsychological syndrome after resection of insular tumor.

The first group consisted of 11 (21.5%) patients with similar pre- and postoperative neuropsychological status. There were 4 patients with left-sided tumor and 7 ones with right-sided tumor. Thus, postoperative cognitive impairment was less common in patients with right-sided neoplasm. Mild impairment of auditory-speech memory was observed prior to surgery in patients without significant postoperative cognitive impairment. Elements of efferent motor aphasia were detected in 1 patient with Gr IV tumor.

Partial resection of insular tumor was performed in 3 out of 11 patients that resulted their stable state after surgery. Eight patients underwent complete excision of the insula without significant trauma to surrounding brain matter (on the left in 2 patients, on the right in 6 patients). There were low grade tumors in these patients. Two observations were of particular interest because total resection of insula on the left did not lead to changes in either memory or speech (Fig. 1).

Our data are very important. It was shown that resection of insular tumor (including left-sided neoplasm) without concomitant injury of adjacent mediobasal parts of the frontal and temporal lobes may be associated with no cognitive disorders (including memory and speech).

The next group of patients (n=11, 21.5%) showed moderate postoperative aggravation of neuropsychological symptoms. Left-sided tumor was diagnosed in 8 patients, right-sided neoplasm — in 3 cases. Ten patients had low-grade gliomas (Gr II, diffuse astrocytomas prevailed). One patient had left-sided glioblastoma with spread to the temporal lobe. In this case, clear preoperative acoustic-mnestic aphasia was determined during neuropsychological examination and postoperative period was characterized by neurological aggravation.

Moderate postoperative cognitive impairment was primarily noted for auditory-speech memory. Visual memory was almost intact. It is important to emphasize that deterioration of auditory-speech memory was noted in patients with left-sided and right-sided tumors, although certain characteristics depended on the side of surgery. In these patients, tumor spread to adjacent parts of the frontal, temporal and parietal lobe (one case) lobes was observed. As a result, postoperative period was characterized by the symptoms typical for these parts of the brain besides mnestic aggravation. For example, one patient with right hemispheric tumor experienced eloquence, euphoria with inappropriate playfulness (dysfunction of the basal parts of the right frontal lobe), another patient - mild spatial disorders during copying (right parietal lobe dysfunction). In patients with left hemispheric tumors, first of all, disorders of auditory-speech memory occurred in postoperative period. These disorders were often characterized by the features characteristic for participation of the left frontal lobe in cognitive defect formation in these patients. Mild anomic aphasia occurred in 3 cases after surgery (elements of acoustic-mnestic temporal aphasia).

Severe postoperative cognitive impairment was noted in the following 2 groups of patients (symptoms de novo or significant deterioration of preoperative disorders).

In one of these groups (8 (15%) patients with left-sided tumor), progressive cognitive impairment may be predominantly caused by tumor spread to the adjacent parts of the brain (temporal and frontal lobes, in three patients — to subcortical nuclei). Aphasia de novo or significant postoperative deterioration was observed in these patients (5 patients with temporal aphasia, acoustic-mnestic, 2 patients with combined aphasia). Significant aggravation of memory disorders occurred in one case. Significant deterioration of modal-nonspecific memory disorders was predominantly typical for auditory-speech sphere. Violation of trace selectivity was often detected in mnestic sphere especially in delayed reproduction, i.e. there was a reproduction of words which were not show. These symptoms are typical for lesion of the frontal lobes16. Memory and speech disorders in these patients were associated with defects of dynamic praxis, motor perseverations, counting difficulties, writing errors in accordance with type of aphasia.

Postoperative aggravation of cognitive impairment in the next group of patients (n=10, 19%) may be explained by local intraoperative complications — postoperative focal ischemia of adjacent brain structures (subcortical nuclei as a rule) and/or blood accumulation within the tumor bed. There were 6 patients with left-sided tumor and 4 patients with right-sided tumor. Glioblastoma was diagnosed in 3 patients, glioma Gr II — in other patients. Postoperative ischemia was confirmed by MRI data in 9 patients from this group and associated with injury of lenticulostriate arteries. Blood accumulation was detected in one patient with right hemispheric tumor. However, disorders of higher mental functions clearly confirmed more severe brain damage.

In this group, patients with left hemispheric tumor had postoperative aphasia with predominant efferent motor component. These disorders were associated with ischemia of subcortical nuclei. In addition, patients with left-sided and right-sided neoplasms had other subcortical symptoms, for example, 3 patients developed subcortical speech disorders (speech became slightly modulated, quiet, dysarthria). There was deterioration of memory disorders, motor perseverations, reduced criticism to own condition (especially after right-sided surgery), poor retention of assignment program by the frontal type in these patients.

The most severe aggravation of cognitive defects combined with severe motor impairment was observed in the last group of patients (n=7, 13%). Five patients underwent surgery for left-sided tumor, two ones – for right-sided tumor. Left-sided surgery was followed by severe aphasia, right-sided intervention - disorientation in time, poor program retention in intellectual tests and significant deterioration of auditory-speech and visual memory. Clinical deterioration was associated with intraoperative injury of middle cerebral artery branches and subsequent hemispheric ischemia with capture of internal capsule.

Thus, typical symptoms of insular tumors are focal ES with olfactory and gustatory hallucinations with vegetative disorders. These clinical features make similar insular tumors and medial neoplasms of temporal lobe. Epileptic seizures were absent in early postoperative period.

Memory disorders is predominant neuropsychological finding in preoperative period. Resection of insular tumors (even in patients with left-sided lesion) is not necessary followed by postoperative cognitive impairment including memory and speech defects. In our opinion, the absence of progressive speech and memory impairments cannot be explained by functional compensation in patients with long history of tumor growth because injury of the classical speech areas in patients with low grade tumors results aphasia. Postoperative memory and speech disorders are observed even in case of mild spread of tumor to adjacent cerebral areas (mediobasal parts of the frontal and temporal lobes). Severity of these disturbances directly depends on the grade of tumor spread to adjacent parts of the brain.

Intraoperative vascular complications are followed by postoperative cognitive impairment in accordance with affected vascular pool.