Filippo Baldacci

Mild cognitive impairment and cognitive-motor relationships in newly diagnosed drug-naive patients with Parkinson's disease

Background and aims (1) To establish the prevalence of mild cognitive impairment (MCI) in newly diagnosed drug-naive patients with Parkinsons disease adopting recently proposed and more conservative preliminary research criteria. (2) To investigate the relation between cognitive performances, MCI and motor dysfunction. Methods 132 consecutive newly diagnosed drug-naive PD patients and 100 healthy controls (HCs) underwent a neuropsychological evaluation covering different cognitive domains. Moreover, on the basis of the Unified Parkinsons Disease Rating Scale II/III, different motor scores were calculated and patients were classified in motor subtypes. 11 patients were excluded from the analysis during clinical follow-up which was continued at least 3u2005years from the diagnosis; therefore, the final sample included 121 patients. Results MCI prevalence was higher in PD (14.8%) patients than in HCs (7.0%). PD patients reported lower cognitive performances than HCs in several cognitive domains; HCs also outperformed cognitively preserved PD patients in tasks of episodic verbal memory and in a screening task of executive functions. MCI-PD patients presented a more severe bradykinesia score than non-MCI PD patients and patients mainly characterised by tremor had better performances in some cognitive domains, and specific cognitive-motor relationships emerged. Conclusions Although the adoption of more conservative diagnostic criteria identified a lower MCI prevalence, we found evidence that newly diagnosed drug-naive PD patients present a higher risk of MCI in comparison with HCs. Axial symptoms and bradykinesia represent risk factors for MCI in PD patients and a classification of PD patients that highlights the presence/absence of tremor, as proposed in this study, is probably better tailored for the early stages of PD than classifications proposed for more advanced PD stages.

Progression of brain atrophy in the early stages of Parkinson's disease: A longitudinal tensor‐based morphometry study in de novo patients without cognitive impairment

The presence of brain atrophy and its progression in early Parkinsons disease (PD) are still a matter of debate, particularly in patients without cognitive impairment. The aim of this longitudinal study was to assess whether PD patients who remain cognitively intact develop progressive atrophic changes in the early stages of the disease. For this purpose, we employed high‐resolution T1‐weighted MR imaging to compare 22 drug‐naïve de novo PD patients without cognitive impairment to 17 age‐matched control subjects, both at baseline and at three‐year follow‐up. We used tensor‐based morphometry to explore the presence of atrophic changes at baseline and to compute yearly atrophy rates, after which we performed voxel‐wise group comparisons using threshold‐free cluster enhancement. At baseline, we did not observe significant differences in regional atrophy in PD patients with respect to control subjects. In contrast, PD patients showed significantly higher yearly atrophy rates in the prefrontal cortex, anterior cingulum, caudate nucleus, and thalamus when compared to control subjects. Our results indicate that even cognitively preserved PD patients show progressive cortical and subcortical atrophic changes in regions related to cognitive functions and that these changes are already detectable in the early stages of the disease. Hum Brain Mapp 35:3932–3944, 2014.

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Levodopa response in dementia with lewy bodies: A 1-year follow-up study

PURPOSEnTo evaluate levodopa responsiveness in patients with probable dementia with Lewy bodies (DLB) compared to early Parkinsons disease (PD) patients.nnnMETHODSnTwenty four cases with DLB and 21 with PD underwent a baseline assessment with UPDRS (sub-item II and III) and an acute levodopa challenge test. Positive response to acute levodopa test was defined as an improvement of at least 15% in the tapping test, and at least 25% in the walking test and rigidity or tremor score. Subsequently, all patients were treated continuously with levodopa and evaluated after 6 and 12 months by means of UPDRS II/III.nnnRESULTSnPositive response to the acute levodopa test was observed in 55% of DLB patients (acute DLB responders), and in 90% of PD patients (acute PD responders). Acute DLB responders showed increased latency, and reduction of both duration and amplitude of response to acute levodopa in comparison with acute PD responders. At the 6-month follow-up visit, acute DLB responders showed a greater motor benefit compared with acute DLB non-responders. This improvement was similar to that observed in PD patients. However, at 1-year follow-up acute DLB responders showed a faster worsening of UPDRS III scores compared with acute PD responders, implying a reduction of levodopa efficacy.nnnCONCLUSIONSnPositive response to acute levodopa test can occur in DLB patients and may be predictive of long-term benefit of chronic levodopa therapy, although the motor improvement is less impressive than in PD patients.

Nummular headache dramatically responsive to indomethacin

Dear Sir Nummular headache (NH) may be considered as primary neuralgia characterized by focal pain in a single round or elliptical area of the head surface (1). The pain is unilateral, usually chronic and mild to moderate in intensity, with exacerbations that are often superimposed on a baseline pain (2). We report a case of NH with complete responsiveness to indomethacin. A 40-year-old man came to our observation with a six month history of focal head pain in the right parietal region. His past medical history was unremarkable. The headache beganwithout any precipitant. The affected area was perfectly circular, with a 3 cm diameter. The pain was continuous, dull and pressing, graded 2–3 out of 10 in intensity on a 10-point verbal numeric scale (VNS), with one or two daily exacerbations lasting hours and characterized by a stabbing ache graded 5–7 by VNS. The affected area was occasionally tender to the touch. Neurological examination was completely negative, as well as routine blood tests, including erythrocyte sedimentation rate and screening for immunological disorders. The patient underwent both computed tomography and MRI scans of the brain, which proved normal. The patient tried paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and ketoprophene, with no or partial relief. Amitriptyline 30mg/day for one month, gabapentin 900mg/day for one month and dexamethasone 8mg/day intramuscular (IM) for 10 days were used without benefit. An Indotest (3) (indomethacin 50mg IM) was performed, with complete pain relief after just approximately 45 minutes. Hence, trial with indomethacin per os (25mg BID) provided complete pain relief. After two weeks’ treatment, the indomethacin trial was stopped, but the pain recurred with the same characteristics within few days. Thus, the trial was restarted, again with a prompt response. After one month, the medication was definitely discontinued and the patient remained pain-free during two months follow-up. Only a few cases of NH have been reported to date, and not much is known about NH treatment. The sharply delimited borders of the painful area suggest a peripheral cause; possible mechanisms proposed are a neuropathy of a terminal branch of a cutaneous scalp nerve and a focal, nociceptive-type pain stemming from epicranial tissues (2). According to the hypothesis of a neuropathic origin of the pain in NH, the drugs which usually work in neuropathic pain have been the most broadly used as prophylaxis; however, especially in cases of moderate-to-severe pain, response to treatment is often unsatisfactory, as previously reported by Ruscheweyh et al. (4). Our case report fulfills the proposed diagnostic criteria for NH (1), and a complete response to indomethacin was observed. Indomethacin responsiveness in NH has been appropriately investigated in only few cases, with contradictory results (4–7). NH is one of the strictly unilateral headaches, and its responsiveness to indomethacin may raise the question of whether NH could share not only clinical but also pathogenetic features with other strictly unilateral headaches which are indomethacin responsive. The indomethacin-responsive headaches seem to have a central origin of pain; to the contrary, in NH the source is supposed to be peripheral, although a possible central contribution cannot be excluded. As discussed above, NH may be resistant to the medical therapy commonly used in neuropathic pain, and recently a relationship between NH and menstrual hormone variations has been reported (8). The clinical points here are (1) indomethacin could be a valid alternative approach in clinical practice; in fact, some patients have been reported to partially respond to this treatment and we report a case with dramatic response; and (2) Indotest, in our patient, turned out to be a useful and easy-to-use tool to detect an early-indomethacin-responder patient.

‘Indotest’ in Atypical Hemicrania Continua

Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) was performed. In all three cases INDOTEST predicted chronic responsiveness to indomethacin. Thus, in cases of HC with atypical features, INDOTEST could help for a correct diagnosis and therapy.

Prevalence of right–to–left shunt in patients with cluster headache

Recent investigations documented that the prevalence of right–to–left shunt (RLS) in patients with migraine with aura (MA) is significantly higher than in healthy controls and similar to prevalence of RLS in young patients with cryptogenic stroke (CS). Nevertheless, little data are available in the literature about RLS prevalence in the other forms of primary headache. The aim of this study was to investigate the occurrence of RLS in patients with cluster headache (CH). We enrolled 30 consecutive patients with CH diagnosis according to the IHS criteria and 40 controls. RLS was assessed with bilateral transcranial Doppler contrast (TCDc) monitoring of middle cerebral arteries. Eleven patients (37%) resulted positive to TCDc monitoring for evaluation of RLS. These data show that the presence of RLS in this group is more prevalent than in the general population and similar to that found in MA and in CS.

Migraine features in migraineurs with and without anxiety-depression symptoms: a hospital-based study.

BACKGROUNDnMigraine, anxiety and depression often coexist. A neurolimbic model of migraine has been recently proposed accounting for a dynamic influence of pain, mood and anxiety on the migraine disease. However, very few data exist concerning clinical migraine features in patients reporting anxiety-depression symptoms.nnnOBJECTIVEnAim of our study was to test differences in clinical migraine features between migraineurs with anxiety-depression symptoms and migraineurs without ones.nnnMATERIALS AND METHODSnWe recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, triggers, allodynia. Anxiety and depression symptoms were evaluated in each patient by two brief self-reported scales: the generalized anxiety disorder 7-item scale (GAD-7) and the Patient Health Questionnaire 9-item scale (PHQ-9). A cut-off of 5 in both the GAD-7 and the PHQ-9 was considered positive for the presence of anxiety-depressive symptoms.nnnRESULTSnOne hundred and one patients (51.5%) had anxiety-depression symptoms (GAD-7 and PHQ-9 ≥ 5). They reported a more headaches/month (p = 0.004), higher number of triggers (p < 0.001), and were more allodynic (p = 0.005). In a binary logistic regression model triggers and allodynia made a unique statistical contribution on reporting anxiety-depression symptoms.nnnCONCLUSIONnOur results showed that the presence of anxiety-depression symptoms affects migraine clinical presentation. They are associated with enhanced migraine triggers susceptibility, more ictal allodynic symptoms as well as more headaches/month. An altered sensation in migraineurs with anxiety-depression symptoms could be a result of a lower pain threshold and an increased cortical excitability in a broader context of a neurolimbic dysfunction.

Peri-ictal prolonged atrial fibrillation after generalized seizures: Description of a case and etiopathological considerations

Cardiac rhythm changes are not uncommon in connection with seizures and should be considered and recognized given their potentially harmful consequences including Sudden Unexpected Death in Epilepsy (SUDEP). The most well known are ictal tachycardia and bradycardia. However, other potentially dangerous peri-ictal arrhythmias have been reported. Brief atrial fibrillation episodes, never longer than 2 min, have rarely been described in connection with seizures. We report the case of a patient who presented with two generalized tonic-clonic seizures associated with prolonged atrial fibrillation. Extensive non-invasive cardiac investigations failed to disclose cardiac abnormalities, and after proper antiepileptic drug treatment the patient had neither further seizures nor cardiac events in an 18-month follow-up. Our case, to our knowledge, is the first report of prolonged (more than 1 h) peri-ictal atrial fibrillation.

Postpartum Headache Due to Spontaneous Cervical Artery Dissection

Postpartum headache is quite common and often related to potentially ominous cerebrovascular accidents. As illustrated in previously published reports, spontaneous cervical artery dissection is a rare but possible cause of headache in the postpartum. We provide 2 additional cases to the 19 described so far, including the first ever report of migraine with aura‐like symptoms. Additionally, we summarize the literature and we speculate about the possible etiopathological mechanism underlying this condition.