Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity.

Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer's disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be "subjective," but rather a specific and defined clinical entity.

Anosmia predicts memory impairment in post-COVID-19 syndrome: results of a neuropsychological cohort study.

Recovered COVID-19 patients frequently suffer of cognitive disorders. Several etiopathogenetic mechanisms have been considered for the brain complications in COVID-19 but results are uncertain. Amongst them, an olfactory route to SARS-CoV-2 brain infection might explain cognitive and memory disturbances in post-COVID-19 patients, given the cooccurrence of anosmia and possible underlying limbic involvement. The aims of the study are to investigate cognition of patients with post-COVID-19 syndrome, and to find clinical factors predicting cognitive and memory impairments. 18 patients with post-COVID-19 syndrome underwent neuropsychological assessment and evaluation of clinical parameters. Stepwise regression analysis was used between clinical parameters as factors and cognitive global scores as dependent variables. Since only anosmia predicted memory performances, repeated measures ANOVA of memory scores was conducted between anosmic and non-anosmic patients. We found lack of association between clinical parameters and cognitive performances. Only anosmia was a good predictor for memory performances, with anosmic subjects showing a temporo-mesial amnesic profile. Our study shows novel findings of causal association between transient anosmia during COVID-19 and memory disorders with temporo-mesial dysfunction, probably sharing a common pathophysiological mechanism, and suggesting a possible SARS-CoV 2 infection of the limbic brain via the olfactory route. In contrast to previous studies, cognitive dysfunctions were not associated with respiratory distress, comorbidity, and depression.

Improving Amnesia Diagnostic Accuracy with RAVLT Single Scores and Composite Indices: Italian Normative Data.

OBJECTIVE: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used verbal memory measure that provides scores for different aspects of memory. It involves repeated auditory presentation and recall of a 15-item word list (List A) followed by presentation and recall of a distractor list (List B) and then un-cued immediate and delayed recalls (at 15 min and 1 week) of List A as well as recognition testing. Aims of this study are to provide Italian normative data for certain RAVLT Scores and Composite Indices to improve the diagnostic accuracy of the test in clinical settings and to provide further evidence on how RAVLT can differentiate different amnesia profiles due to focal lesions. METHODS: We enrolled 440 healthy participants and RAVLT Single Scores and Composite Indices have been analyzed by means of multiple regression to verify the influence of age, education, and gender. RESULTS: We computed the best linear models with RAVLT Single Scores and Composite Indices, as dependent variables, and the most suitable transformation of independent variables. By reversing the signs of the regression coefficients, the adjustment factors for each level of age and, if needed, education and gender have been computed and the adjusted scores have been standardized into Equivalent Scores. CONCLUSION: Using these standardized measures, we differentiate three profiles of amnesia due to selective hippocampal sclerosis with severe encoding deficit, fornix lesions with source memory problems, and temporal lobe epilepsy with consolidation failure.

Dural Arteriovenous Fistula as a Reversible Cause of Progressive Parkinsonism and Dementia: A Case Report.

A dural arteriovenous fistula (DAVF) is an abnormal direct connection between an intracranial artery and the dural venous sinus. In rare cases, DAVF might show rapidly progressive dementia onset with extrapyramidal signs, often misdiagnosed as Parkinson disease or vascular parkinsonism and, therefore, pharmacological treatments are ineffective. Here, we report the case of 84-year-old man with rapidly progressive parkinsonism and dementia who was initially treated with levodopa without any improvement. Approximately 8 months following the symptom onset, a magnetic resonance (MR) imaging of the brain revealed bilateral and symmetrical hyperintensity of the white matter on both cerebral hemispheres on T2-weighted images. Three-dimensional and post-contrast T1-weighted images showed a subtentorial ovalar area with venous drainage alteration, and hypertrophic left occipital artery direct to venous sac. The angiography study confirmed a diagnosis of DAVF. Endovascular treatment by cook pressure technique successfully provided fistula obliteration. The patient rapidly recovered after the endovascular treatment, with restitutio ad integrum of cognitive functioning and resolution of extrapyramidal syndrome. Approximately 1 year after the endovascular treatment, a brain MR scan with angiogram-MR sequences showed almost complete disappearance of white matter alterations on both cerebral hemispheres, and normal visualization of venous system.

Late-onset obsessive-compulsive disorder as the initial manifestation of possible behavioural variant Alzheimer's disease.

INTRODUCTION: A late-onset obsessive-compulsive disorder (OCD) might be a challenging diagnostic issue because of the overlapping with the dementia conditions more related to frontal lobe pathology. We aim to describe and investigate how this condition might represent the isolated long-lasting symptomatology of a frontal Alzheimer's disease (AD). METHODS: An elderly woman with normal cognitive status showed a subacute onset of OCD with contamination obsession and washing compulsion. We conducted neuropsychological assessments and neuroimaging examinations at the onset and at 3-years follow-up. RESULTS: At 3-years follow-up, the patient developed cognitive deterioration, frontal behavioural disorders and improvement of OCD. Cognitive assessment showed impairments of executive functions, episodic memory, and constructional apraxia, according to the involvement of fronto-mesial, temporal and parietal regions at neuroimaging. A clinical diagnosis of possible behavioural variant AD was assigned. CONCLUSION: A typical OCD might be the long-lasting initial manifestation of a possible behavioural variant AD due to dysfunctions of the anterior cingulate network.

Early stage glioblastoma: retrospective multicentric analysis of clinical and radiological features.

OBJECTIVES: The aim of this study was to report our experience with early stage glioblastoma (e-GB) and to investigate the possible clinical and imaging features that may be helpful to the radiologist to correctly diagnose this entity. METHODS: We performed a retrospective research of patients diagnosed with glioblastoma at two hospitals during a 10-year period. We reviewed all pre-operative MR and included only patients with early stage GB lesions, characterized by hyperintense on T2-weighted signal, with or without contrast-enhancement at post-contrast T1-weighted images, without "classic" imaging appearance of GB (necrosis, haemorrhage, oedema). All preoperative MR were evaluated by an experienced neuroradiologist and information on patients' demographics, clinical presentation, follow-up, and histopathology results study were collected. When available, preoperative CT examination was also evaluated. RESULTS: We found 14 e-GBs in 13 patients (9 males, 4 females, median age 63 years) among 660 patients diagnosed with GB between 2010 and 2020. In 10 lesions, serial imaging revealed the transformation of e-GB in classic glioblastoma in a median time of 3 months. Clinical presentation included stroke-like symptoms, vertigo, seizures and confusion. Preoperative plain CT was performed in 8/13 cases and in 7 e-GBs presented as a hyperdense lesion. Ten out of 14 lesions transformed in classic GB before surgical intervention or biopsy. All lesions revealed typical immunohistochemical pattern of primary glioblastoma. CONCLUSIONS: E-GB is a rare entity that can often lead to misdiagnosis. However, the radiologist should be aware of its imaging appearance to suggest the diagnosis and to request close imaging follow-up, hopefully improving the prognosis of this very aggressive disease.

Beyond the bipolar disorder diagnosis: Hypothalamus and its network damage in determining neuropsychiatric and Korsakoff-like memory disorders.

Craniopharyngiomas (CP's) are hypothalamic tumors often associated with psychological disorders. Nevertheless, its diagnosis is still challenging when psychiatric disorders are not associated with any other neurological symptoms. This single-case study describes a patient with a history of bipolar disorder before a diagnosis of a large CP arising the sellar and suprasellar region was posed. At the time of the present study the patient showed emotional/behavioral disorders and Korsakoff-like amnesia, that completely recovered after surgical resection of the tumor. This is one of those few cases described in literature, who presented cognitive/behavioral disorders because the compression of the diencephalic structures due to CP mass effect. This case offers further evidence on the functional neuroanatomy of the hypothalamus and its pathways.

Ozone-induced encephalopathy: A novel iatrogenic entity.

BACKGROUND AND PURPOSE: Ozone-based treatments can be associated with central nervous system toxicity, which we have termed ozone-induced encephalopathy (OIE). A detailed description of its phenotype is lacking. METHODS: Three cases with findings suggestive of OIE are presented, and the literature is reviewed. RESULTS: Case 1 is a healthy 59-year-old man presenting with loss of consciousness, cortical blindness, restlessness, and anterograde amnesia immediately following a cervical ozone-therapy (OT) session for chronic neck pain. Brain magnetic resonance imaging (MRI) on admission was normal. A follow-up scan demonstrated a subtle increased T2 fluid-attenuated inversion recovery signal within the left cerebellum; an echocardiography showed a patent foramen ovale (PFO). Case 2 is a 56-year-old woman with history of migraine, PFO, and lumbar pain who presented with headache, bilateral visual impairment, motor dysphasia, and agitation. All her symptoms began immediately after lumbar OT. Her brain MRI was negative. Case 3 is a healthy 27-year-old man who complained of vertigo and mild blurred vision 5 min following a cervical ozone injection. His neurological examination and brain MRI were normal. All three patients had full recovery within 48 h. We found eight additional cases of OIE in the literature. CONCLUSIONS: OIE should be considered in patients presenting with neurological symptoms in close relation to OT. OIE is likely a novel iatrogenic entity with a complex pathogenesis; it is probably underreported because it mimics other neurological conditions.

Progressive aphasia, apraxia of speech and agraphia in corticobasal degeneration: A 12-case series clinical and neuropsychological descriptive study.

BACKGROUND: Despite initial underreporting of language dysfunctions in corticobasal syndrome (CBS), aphasia is now recognized as a frequent feature of this disease. Aphasia in CBS seems clinically overlying to a non-fluent/agrammatic primary progressive aphasia (nfaPPA), which is also a clinical phenotype associated with corticobasal degeneration (CBD) pathology. However, the clinical features of aphasia in CBS still remain poorly delineated, resulting in misjudgements in the differential diagnosis from a PPA presentation of the disease. AIMS: To investigate the language disorders of this syndrome, also through a systematic examination of recoding skills (reading, written spelling and repetition) and articulatory disturbances, which have been rarely examined in previous studies. METHODS & PROCEDURES: We present a clinical and neuropsychological descriptive study of the language impairments in a case series of 12 aphasic patients with a clinical diagnosis of CBS. Language assessment was conducted by means of the Esame NeuroPsicologico dell'Afasia, a comprehensive Italian battery for language functions, the Token Test, and the Apraxia of Speech Rating Scale. OUTCOMES & RESULTS: The language profile of the patients showed a severe expressive language disorder, characterized by non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding and defective sentence repetition. Severe limb apraxia, visual-spatial deficit and alien hand syndrome were also present. Neuroimaging showed bilateral left asymmetric atrophies and hypometabolism in the frontal premotor, parietal posterior and temporal areas. CONCLUSIONS & IMPLICATIONS: These findings suggest that aphasia in CBS might present as a 'mixed PPA', instead of an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA, associated with AoS, stuttering and agraphia, which might be additional important cognitive markers for the clinical diagnosis of CBS and discriminating features of an nfaPPA presentation of a CBD. These results might also suggest specific intervention areas in the rehabilitation of patients with CBS. What this paper adds What is already known on the subject Language disorders in CBS patients usually present clinically overlying to an nfaPPA, which is also a clinical phenotype associated with CBD pathology, according to recent diagnostic criteria. However, the clinical features of aphasia in CBS still remain poorly delineated, and this raises difficulties and misjudgements for clinicians in the differential diagnosis from a PPA presentation of the disease. What this paper adds to existing knowledge This study shows that the language profile of our CBS patients was characterized by severe expressive language disorders, with non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding, and defective sentence repetition. These findings suggest that aphasia in CBS might present as a 'mixed PPA', rather than an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA associated with AoS, stuttering and agraphia. What are the potential or actual clinical implications of this work? These results suggest that AoS, stuttering and agraphia might be important additional cognitive markers for the clinical diagnosis of CBS, and discriminating features of an nfaPPA presentation of a CBD. The language disorders exhibited in the present study might also support speech and language therapists in targeting specific intervention areas in the rehabilitation of patients with CBS.

Spect-neuropsychology correlations in very mild Alzheimer's disease and amnesic mild cognitive impairment.

BACKGROUND: The purpose of this study was to explore the clinical and brain functional abnormalities in patients with mild Alzheimer's Disease (AD) and patients with amnesic Mild Cognitive Impairment (aMCI). METHODS: we used resting spect-neuropsychology correlations method. RESULTS: We found that parieto-temporal associative cortex, mainly involving the inferior parietal lobule, posterior cingulate and middle temporal gyrus, is compromised early in AD. These results suggest that the dysfunction in these areas contributes to cognitive decline in the storage of verbal information, drawing abilities and non-verbal abstract reasoning in AD. The aMCI group showed hypoperfusion primarily involving the frontal areas bilaterally, and this correlated with the impairment in free delayed recall on a verbal memory task. CONCLUSION: Our results underlie the clinical differences between AD and aMCI patients that might reflect the involvement of different degenerative mechanisms in these groups.

Rotigotine effect in prolonged disturbance of consciousness. Brief report of two cases.

Two patients with post-coma reactivation deficiency who showed a "dramatic" response to rotigotine therapy are described. They had suffered from prolonged coma due to lesions in the mesencephalic ventral tegmental area. The authors believe that rotigotine effect in these cases could be due to restoration of dopaminergic transmission in medial frontal areas previously "de-afferented" from the lesions. Some comatous patients may experience a prolonged difficulty in recovering a normal state of consciousness. This phenomenon may be due to dysfunction of amynergic activating pathways connecting brainstem to the frontal cerebral cortex. In particular, dysfunction of dopaminergic pathways from the mesencephalon to the frontal cortical areas may be responsible for clinical pictures characterized by preserved alertness and total loss of interactions with the surrounding environment; the so called "waking coma" cases.

Dopamine agonists can improve pure apathy associated with lesions of the prefrontal-basal ganglia functional system.

Apathy is a common neurobehavioral symptom of other syndromes or a syndrome per se which occurs in a variety of neuropsychiatric disorders. Apathy depends on disruption of emotional, cognitive, and behavioral functions. Six brain-damaged patients were assessed, including five patients with unilateral or bilateral focal lesions of the basal ganglia or the thalamus (showing apathy due to an auto-activation deficit) and one patient with bilateral lesions in the limbic temporomesial cortex associated with a form of emotional-affective apathy. A significant and persistent improvement of apathy was observed in all patients after treatment with dopamine agonists such as pramipexole, ropinirole, and rotigotine. These results confirm preliminary reports on the beneficial effects of dopamine agonist agents on apathy and suggest that this syndrome can be treatable in many cases.

Apathetic syndrome from carotid dissection: a dangerous condition.

Isolated behavioural disturbances can mimic psychiatric diseases and delay diagnosis of acute brain disease. We reported the case of a patient with carotid dissection manifesting only with apathetic syndrome that was initially considered as a possible postpartum depression, causing a threatening diagnostic delay.