An atypical presentation of diffuse midline pontine glioma in a middle age patient: Case report.

INTRODUCTION: Diffuse midline glioma is a newly WHO defined entity (grade IV) (Louis et al., 2016) which includes diffuse intrinsic pontine glioma (DIPG) reported in pediatric population and, occasionally, in young adults. Here, we present a detailed description of an atypical case of diffuse midline glioma in a 53 years old woman. CASE REPORT: A caucasian woman aged 53 from Ukraine, was referred to another neurological department complaining of 3 months history of progressive postural instability and gait impairment with frequent falling. Magnetic resonance demonstrated two brainstem lesions, hyperintense in FLAIR with "patchy" peripheral enhancement, leptomeningeal and cranial nerves enhancement. CSF was normal. Due to positive antinuclear antibodies test (ANA 1:360), intravenous steroid treatment was administered and reported to initially improve the patient condition. However, the following weeks the lady worsened. Imaging features were unchanged. Because quantiferon test resulted positive, MRI-Spectroscopy showed an inflammatory pattern and MRI perfusion study and brain FDG-PET, were normal, tubercolar granulomatous hypothesis was initially favored. Antitubercular therapy with isoniazid, pyrazinamide, ethambutol and rifampicin was started without any clinical improvement. Hence, the biopsy was proposed. The procedure revealed a diffuse midline pontine glioma. Considering the advanced stage of the disease, radiotherapy was not indicated. Patient died after eight months from the onset of neurological disturbances. CONCLUSION: Our case shows that diffuse midline glioma is a CNS tumor not limited to young population but occurring also in middle aged patients with an insidious pattern. We therefore recommend to perform biopsy at very early stages in patients with atypical brainstem lesions.

Is the brain of migraineurs "different" even in dreams?

Migraineurs brain is hyper-excitable and hypo-metabolic. Dreaming is a mental state characterized by hallucinatory features in which imagery, emotion, motor skills and memory are created de novo. To evaluate dreams in different kinds of headache. We included 219 controls; 148 migraineurs (66 with aura-MA, 82 without aura-MO); 45 tension type headache (TTH) patients. ICHD-II diagnostic criteria were used. Ad hoc questionnaire was used to evaluate oneiric activity. The Generalized Anxiety Disorder Questionnaire, and the Patient Health Questionnaire were administered to evaluate anxiety and mood. The prevalence of dreamers was similar in different groups. Frequency of visual and auditory dreams was not different between groups. Migraineurs, particularly MA, had an increased frequency of taste dreams (present in 19.6 % of controls, 40.9 % of MA, 23.2 % of MO, 11.1 % of TTH, p < 0.01), and of olfactory dreams (present in 20 % of controls, 36 % of MA, 35 % of MO and 20 % of TTH, p < 0.01). Anxiety and mood did not influence these results. The increased frequency of taste and olfactory dreams among migraineurs seems to be specific, possibly reflecting a particular sensitivity of gustative and olfactory brain structures, as suggested by osmofobia and nausea, typical of migraine. This may suggest the role of some cerebral structures, such as amygdala and hypothalamus, which are known to be involved in migraine mechanisms as well in the biology of sleep and dreaming.

Blood pressure during nocturnal sleep in headache.

AIM: Interactions between blood pressure control, sleep and headache have been largely studied, although not well understood. We designed a study trying to simultaneously evaluate all three aspects in the same subjects. We particularly concentrated on the observation of physiological blood pressure circadian rhythm, and the presence of cutaneous allodynia correlated to headache. Objective of the study was to investigate blood pressure during nocturnal sleep in patients that underwent a blood pressure 24 hours monitoring, and at the same time the presence of headache and of sleep behavioural alterations. METHODS: Blood pressure 24 hours monitoring was performed by an ambulatory blood pressure (ABP) monitor (Space Labs) with its ad hoc software. Headache diagnosis was made according to ICHD-II criteria. Presence of allodynia and sleep behavior were evaluated through semi-structured ad hoc questionnaires. RESULTS: A total of 195 subjects were included, of which 122 without headache (mean age 60.4±11.6 years, 78 men and 44 women) and 73 with history of headache, (mean age 54.2±12.5 years, 18 men and 55 women). Fifty-one headache patients had migraine (mean age 52.6±11.7 years, 11 men and 40 women) and 22 tension type headache (TTH - mean age 58.0±13.5 years, 7 men and 15 women). Allodynia was found in 30 out of 73 headache patients: 23 out of 51 in the migraine group and in 7 out of 22 in the tension-type one. The physiological reduction of blood pressure during night (dipping) was more conserved among headache patients (34 dippers out of 73 subjects, 46,6%) with respect to subjects without headache (40 dippers out of 122, 32,8%) and that this border-line difference was more strongly significant comparing allodynic subjects (19 dippers out of 30, 63.3%) with both non-headache (40 dippers out of 122, 32.8%, P<0.001) and non-allodynic (15 out of 43, 34.9%, P<0.05) ones. No significant difference was observed between headache patients and subjects without headache in terms of mean systolic and diastolic pressure, neither between migraine and TTH. CONCLUSION: Allodynic headache patients seem to maintain a more physiologic pressure circadian rhythm. While considering the possibility of selection bias, the hypothesis of an allostatic function of headache and allodynia in patients with unbalanced blood pressure could be made.

Possible correlations between blood pressure, primary headaches and cutaneous allodynia.

Following an allostatic perspective, episodic migraine (M) may be considered as an adaptive behavioural response to endogenous or exogenous stressors, while its progression to a daily or nearly daily form (chronic migraine) may represent the failure of adaptive strategies. Multiple factors may enhance the progression/chronification of M, and among these the presence of cutaneous allodynia (CA) as well as alterations in blood pressure and in sleep. The working hypothesis of the study was that subjects with M, and particularly those with CA, could show a tendency towards high blood pressure levels and/or to alterations in the circadian rhythm of blood pressure. We studied 235 subjects consecutively attending a centre for blood pressure control for a blood pressure 24 h monitoring. Headache diagnosis was made according to the ICHD-II criteria. The presence of CA was evaluated through a semi-structured ad hoc questionnaire. Blood pressure 24 h monitoring was performed by an ambulatory blood pressure monitor (Space Labs) with its ad hoc software. Seventy-eight subjects had a history of headache (mean age 54.0 ± 12.4 years, 18 men and 60 women); 56 of them had M, 22 had tension-type headache; among them, CA was found in 24/56 subjects with M, and in 6/22 with tension-type headache; 157 subjects did not suffer from headache (mean age 60.5 ± 11.5 years, 99 men and 58 women). No significant difference was observed between headache subjects and subjects without headache in terms of mean systolic and diastolic pressure, neither in the M nor in tension-type subgroups. With regard to the circadian rhythm of blood pressure, the physiological reduction during night (dipping) was more evident among headache subjects than in subjects without headache; this border-line difference was more strongly significant in subjects with CA than both non-headache (p = 0.003) and non-CA (p = 0.05) ones. The difference between allodynic and non-allodynic subjects was present also in the M sub-group (7 dippers out of 32 non-allodynic migraineurs vs. 12 dippers out of 24 allodynic migraineurs, p = 0.03) notwithstanding the reduction of the sample size. Despite the initial hypothesis, subjects with primary headaches did not show differences in terms of mean blood pressure values and they showed a more physiologic blood pressure daily rhythm than those without headaches. Also the presence of CA, a marker of progression to chronic headache forms, was associated neither with hypertension nor with increased frequency of loss of dipping. M, particularly when associated with allodynia, may improve breathing during nocturnal sleep and consequently counteract possible blood pressure alterations, suggesting an allostatic function of allodynic headache.

Possible relationships between headache-allodynia and nocturnal sleep breathing.

Sleep and headache are linked in a bidirectional way. Breathing quality during sleep may be a possible link between them. The objective of this study were to evaluate the prevalence of headache--and of allodynia--in a population of subjects who underwent cardiopulmonary monitoring during sleep for presumed respiratory problems; to evaluate the possible relationships between the presence of headaches--and of allodynia--and respiratory parameters. We studied 181 subjects, 112 without headache (mean age 59.4 ± 13.1 years, 97 men and 15 women); 69 with history of headache (42 men and 27 women; 41 migraineurs and 28 with tension type headache). Headache diagnosis was made according to ICHD-II criteria. A semi-structured ad hoc questionnaire was used to evaluate the presence of allodynia. Full cardiopulmonary monitoring was performed by SOMNO check(®) effort (WEINMANN) with SaO(2), T90 and AHI determination. Headache and headache-associated allodynia were particularly frequent in this population, suggesting a positive correlation between breathing problems during sleep and head pain, and allodynia. The observation that better respiratory parameters were found among headache sufferers with respect to those without headache, even in allodynic subjects, seems to reverse this point of view: headache and allodynia may possibly have an allostatic function preventing deep sleep and, in turn, avoiding prolonged apneas.

Correlation between presence of allodynia and sleep quality in migraineurs.

Cutaneous allodynia is a frequent complaint in migraine patients, possibly induced by central sensitisation of trigeminal nucleus. The objective of this study is to investigate if sleep quality is related to the presence of migraine-associated allodynia. A total of 175 consecutive migraineurs were included, 124 with episodic and 51 with chronic forms. As control group, 73 subjects free from any kind of headache were included (HC). The presence of allodynia and sleep disturbances was assessed by a set of semi-structured questions. Chi-square test was applied to compare frequencies among groups. Sleep quality was worse among migraineurs with respect to controls for each sleep item analysed. This difference was significant for all items but one (i.e. frequency in drug use to induce sleep). The frequency of sleep disturbances was higher than in controls in both allodynic and non-allodynic migraineurs, although statistical analysis showed that all these differences were still significant in allodynic migraineurs (also in this case for all the sleep items but one, i.e. frequency in drug use to induce sleep), whilst non-allodynic migraineurs were significantly different from controls only for one item (frequency of initial insomnia). These results suggest that allodynia is strongly related to sleep quality, in a bi-directional way: sleep disturbances may favour central sensitisation, and, in turn, allodynia may impair sleep.