Chronic obstructive pulmonary disease may complicate Alzheimer's disease: a comorbidity problem.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) may be associated with worsening of cognitive performance. We studied patients with Alzheimer's disease (AD) with and without COPD, and we analyzed, in a retrospective way, clinical and neuropsychological variables to verify if COPD plays a pejorative role on cognitive or functional autonomy in patients with dementia. METHODS: We enrolled 23 adult patients (AD-COPD) with probable AD and COPD and 23 with AD only (AD-only); they were matched for sex, age, educational level, and Mini Mental State Examination (MMSE) at the disease onset. Global cognitive status was estimated using MMSE at the first assessment and after 24 months. Memory, executive functions, praxia, and language were the other cognitive domains analyzed. The two groups were also compared for the presence of behavioral disorders (anxiety, depression). RESULTS: AD-COPD had worse results in executive functions screening than AD-only; no significant differences were found comparing other cognitive domains; moreover, there was no significant difference between the two groups considering the decrease in MMSE scores. AD-COPD also showed a higher presence of depression. DISCUSSION: COPD is known to be associated with the development of cognitive deficits, in particular, regarding for executive functions and attention, memory and logical reasoning. In this context, MMSE has a low diagnostic accuracy to underline effective cognitive impairment in AD-COPD. Our study shows a higher frequency of frontal deficits and behavioral disturbances in patients with AD and COPD than patients with AD-only. COPD could complicate the management of AD patients, thus necessitating a closer and multidisciplinary monitoring.

Frontotemporal Dementia Presenting as Gambling Disorder: When a Psychiatric Condition Is the Clue to a Neurodegenerative Disease.

Behavioral variant frontotemporal dementia, the most common form of frontotemporal dementia, is characterized by executive dysfunction and changes in personality and behavior, sometimes with associated psychiatric disorders. We report a man who suddenly developed a gambling disorder when he was 55 years old. A year later he developed personality changes of agitation, euphoria, and disinhibition, along with binge eating and dysthymia. He did not improve on paroxetine 40 mg/day. Two years after the onset of his symptoms, he came to our clinic for evaluation. Neuropsychological testing showed deficits in cognitive control, planning, and attention. Brain magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans showed predominant frontal and temporal alterations, worse in the right hemisphere than the left. Cerebrospinal fluid analysis was not compatible with Alzheimer disease. On the basis of current criteria, we gave him a diagnosis of probable behavioral variant frontotemporal dementia presenting with a psychiatric symptom. Our findings in this unusual patient confirm the importance of close clinical monitoring in people who have a psychiatric disorder with atypical features, because the condition may mask an underlying neurodegenerative disease.

Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report.

BACKGROUND: Frontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia. We describe the case of an FTD behavioural variant with a psychiatric presentation and a normal neurological examination, due to a C9Orf72 gene mutation. CASE PRESENTATION: The patient was a 57 years-old Caucasian woman with a recent onset of bizarre behaviours and mystic delusions. She had a negative clinical history for previous psychiatric disorders and treatments and this was her first admission to a Psychiatry Ward. A careful assessment was performed including, beyond psychiatric evaluation, the following: blood sampling, neurological examination (including electroencephalogram, electroencephalogram with zygomatic electrodes, Positron Emission Tomography, Cerebrospinal Fluid Analysis), carotid artery Doppler ultrasound, brain Magnetic Resonance Imaging - angio Magnetic Resonance Imaging. Blood sampling for the genetic assessment of mutations associated to primary dementias was performed as well: the genes investigated were FUS, C9Orf72, PSEN-1, PSEN-2. CONCLUSIONS: Serological tests were negative, neurological examination was normal, instrumental examinations showed theta waves in the posterior temporal areas bilaterally and frontotemporal cortical atrophy bilaterally. The genetic assessment of mutations associated revealed she carried a GGGGCC hexanucleotide repeat expansion (at least 80 repeats) in C9Orf72 intron 1. Patients carrying the C9Orf72 mutation are likely to receive a psychiatric diagnosis (mainly mood disorder or schizophrenia) prior to correct diagnosis; this may be particularly problematic for those patients with no neurological signs to orientate diagnosis. Understanding the manner in which such FTD variant may present as a psychiatric syndrome, with a negative neurological examination, is essential to provide the best treatment for patients, as soon as possible, especially when the behavioural anomalies interfere with their care.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

Corpus callosum abnormalities in Tourette syndrome: an MRI-DTI study of monozygotic twins.

BACKGROUND: Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterised by the presence of multiple motor and phonic tics. Recent brain imaging investigations with diffusion tensor imaging (DTI) techniques found reduced measures of connectivity in the corpus callosum of children with TS compared with healthy controls, thus raising the hypothesis that the reduced interhemispherical connectivity in TS reflects neural plasticity processes. METHODS: We assessed corpus callosum white-matter connectivity with fractional anisotropy (FA) index from magnetic resonance-DTI in two monozygotic twins (male sex; age 20) discordant for the diagnosis of TS. RESULTS: Both conventional morphological magnetic resonance images and fibre-tracking reconstruction failed to show any difference between the two twins. On the other hand, mean corpus callosum FA values were significantly lower in the affected twin than in the unaffected twin (p<0.01). The differences in FA values were highest in the posterior portions of the corpus callosum, and lowest in the central area. CONCLUSIONS: Our findings of reduced interhemispherical white-matter connectivity in the affected twin support the hypothesis that plastic remodelling in the corpus callosum possibly represents an adaptation mechanism in TS.

Abnormal postural reflexes in a patient with pontine ischaemia.

The control of body posture is a complex activity that needs a very close relationship between different structures, such as the vestibular system, and the muscle and joint receptors of the neck. Damage of even one of these structures can lead to abnormal postural reflexes. We describe a case of a woman with a left pontine ischaemia who developed a 'dystonic' extensor posture of the left limbs while turned on the right side. This clinical picture differs from previous reports on the subject, and may relate to ischaemic damage of a pontine structure involved in posture control, or of adjacent neural connections to be yet identified. To the best of our knowledge, this is the first case reported in the literature. Clinical examples of an altered interplay between vestibular and neck receptors are rare.

Evidence of pre-synaptic dopaminergic deficit in a patient with a novel progranulin mutation presenting with atypical parkinsonism.

Parkinsonism can be the presenting feature of frontotemporal dementia due to Progranulin (GRN) mutations or develop over the course of the disease, mimicking idiopathic Parkinson's disease or atypical parkinsonism. Here we report on a patient carrying a novel GRN mutation who presented with asymmetric parkinsonism and developed cognitive decline and language alterations two years later. Brain MRI showed mild asymmetric fronto-parietal atrophy. Single-photon emission computed tomography with I123 ioflupane (DAT-Scan) demonstrated reduced tracer uptake in the left putamen. Larger studies are needed to clarify whether presynaptic dopaminergic deficit is present in all GRN mutation carriers or only in those with parkinsonism.

Adult osteomalacia: a treatable cause of "fear of falling" gait.

A 65-year-old man was hospitalized with a gait disorder, obliging him to shuffle laterally(1) (video on the Neurology Web site at www.neurology.org) because of pain and proximal limb weakness. He had a gastrectomy for cancer 7 years previously, with severe vitamin D deficiency; parathormone and alkaline phosphatase were increased, with reduced serum and urine calcium and phosphate. There was reduced bone density (figure). He was mildly hypothyroid and pancytopenic. B12 and folate levels were normal. Investigation for an endocrine neoplasm (CT scan, Octreoscan) was negative. EMG of proximal muscles was typical for chronic myopathy; nerve conduction studies had normal results.

A case of cranial multinevritis: from the onset to the diagnosis of primary neurolymphomatosis.

Neurolymphomatosis (NL) is a rare peripheral or cranial neuropathy caused by non-Hodgkin's lymphoma (NHL). Diagnosis is often delayed and prognosis is poor. The authors described a woman in her 70s with a facial left peripheral palsy, complete right abducent palsy, left hypoacusia and balance deficit. Then she presented with low progressive hyposthenia at four limbs and cognitive impairment, sudden facial right peripheral palsy and complete left abducent palsy. The authors performed brain and spinal MRI, cerebrospinal fluid (CSF) analysis and extensive haematological examinations for infections, autoimmune and neoplastic diseases. All the results were not diagnostic. Only repeating for the third time a spinal tap, CSF presented neoplastic B cells suggestive for large B-NHL. The authors diagnosed primary NL. The patient was treated with R-CHOP but she died 2 months later. In front of rapidly progressive neuropathy, a NL has to be considered performing different examinations, especially and repeating them after a short period.

Posterior alien hand in a left-handed person.

Posterior alien hand syndrome usually involves the non-dominant hand with lesions usually in the right hemisphere. This is the first case in a left-handed person, involving the dominant hand.

Cluster-like headache and idiopathic intracranial hypertension: a case report.

Cluster headache (CH) is a well-defined primary headache syndrome, but cases of symptomatic headache with clinical features of CH have been previously reported. Idiopathic Intracranial Hypertension (IIH) is a secondary headache disorder characterized by headache and visual symptoms, without clinical, radiological or laboratory evidence of intracranial pathology. Both papilloedema and IIH-related headache are typically bilateral, however asymmetrical or even unilateral localizations are described in literature. We report the case of a previously headache-free woman who presented cluster-like headache and asymmetrical papilloedema related to IIH. In our opinion the asymmetrical presentation supports, in this case, the hypothesis of cavernous sinus involvement in the IIH-related cluster-like headache pathogenesis.