Objective: To characterize the phenotypic spectrum of patients with frontotemporal dementia (FTD) carrying the P392L SQSTM1 mutation. Methods: We describe the clinical phenotype of three well-characterized probands carrying the P392L mutation, and review ten previously published FTD cases with the mutation. Results: All three cases were male with a presenile age of onset (52 or 64 years). Case 1 developed an amnestic-anomic syndrome followed by a behavioral variant of FTD (bvFTD). Case 2, with an autosomal dominant family history of dementia, developed a bvFTD associated with parkinsonism. Both cases had Paget's disease of the bone (PDB). Case 3 presented with a semantic aphasia and, years later, developed a hemilateral upper motor neuron disease (MND) (Mills syndrome). Among the ten previously reported cases (four from the same family), bvFTD was the cognitive phenotype in five, but semantic, nonfluent and logopenic aphasic variants, as well as a pure hippocampal amnestic syndrome were also documented. PDB was observed in six cases, two exhibited parkinsonism, and one MND. Neuroimaging findings showed a tendency toward asymmetric temporal/frontal atrophy, sometimes with periventricular white matter signal abnormalities. Only one third of the cases reported a family history of dementia. Conclusions: The P392L mutation exhibits a pleiotropic effect, giving rise to a broad phenotypic spectrum that includes PDB, FTD, amnestic syndrome, parkinsonism, and MND. Penetrance for the different phenotypes is variable and may be influenced by additional factors. The outlined features may encourage healthcare professionals to screen for this gene, even in cases without a clear family history.

Corticobasal syndrome (CBS) is a rare, clinically heterogeneous neurodegenerative syndrome most commonly associated with corticobasal degeneration (CBD), a 4-repeat tauopathy. CBS presents with asymmetric motor and cortical features, but diagnosis remains challenging, as clinicopathologic concordance is imperfect and other conditions such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration (FTLD) can present with similar phenotypes. We report the case of a 55-year-old woman with a four-year history of progressive, right-sided spastic hemiparesis and rigidity. Electroneuromyography (ENMG) revealed isolated upper motor neuron (UMN) findings with no lower motor neuron (LMN) involvement. Brain MRI demonstrated cortical atrophy in perirolandic regions, and dopamine transporter (DaT) SPECT imaging revealed a marked, unilateral presynaptic dopaminergic deficit. No sensory, cerebellar, or autonomic features were observed, and levodopa challenge test yielded no benefit. FDG-PET and tau-PET imaging were not performed due to unavailability at our center. The marked clinical asymmetry, dopaminergic deficit strongly support a diagnosis of CBS. While CBD remains the most probable underlying pathology, differential diagnoses include PSP, AD, multiple system atrophy (MSA), idiopathic Parkinson's disease (PD), and, less likely, Mills syndrome or other UMN syndromes. Mills syndrome was considered due to asymmetric UMN findings but was excluded due to parkinsonism, cortical atrophy, and presynaptic dopaminergic loss. This case underscores the diagnostic complexity of CBS, particularly in resource-limited settings where advanced imaging tools are unavailable. CBS should be considered a leading diagnosis in patients presenting with asymmetric parkinsonism, UMN findings, especially when supported by DaT-SPECT abnormalities. This case highlights the importance of comprehensive clinical evaluation and multimodal imaging in differentiating CBS from other neurodegenerative syndromes.

A 50-year-old man with hypothyroidism was referred for refractory myasthenia gravis (MG). He developed progressive, painless right-sided shoulder and leg weakness, dysphagia, and fatigable diplopia. Acetylcholine receptor (AChR) antibodies were positive. Immunosuppressive therapies provided only transient improvement in oculo-bulbar symptoms, while hemiparesis progressed. Examination showed fatigable ptosis with curtain sign, vertical gaze limitation, and diplopia localizing to left lateral rectus weakness. Upper motor neuron signs included brisk masseteric reflex, right spastic hemiparesis, and hyperreflexia. EMG demonstrated chronic reinnervation in right cervical and lumbosacral regions. MRI revealed T2 hyperintensity in the left upper cervical cord and adjacent medulla without enhancement. A diagnosis of AChR+ MG and Mills' syndrome was made. While MG has previously been reported to coexist with ALS, this is the first known case associated with Mills' syndrome. This highlights the importance of recognizing overlapping autoimmune and neurodegenerative disorders and the need for further research into shared mechanisms.

Mills' syndrome is a rare motor neuron disease characterized by progressive upper motor neuron dysfunction. As the disease advances, there may be manifestations of bulbar involvement, such as dysarthria, dysphagia, and possibly pseudobulbar affect and progression to the contralateral side may occur lately in patients. Since it was first described by Mills in 1900, there are few cases of Mills' syndrome that have been reported in the literature. Here, we present a case, diagnosed as Mills' syndrome, with 5 years of gradually progressive weakness and stiffness in her left-side limbs with recently added difficulties in speech. Neurological examination revealed bilateral asymmetrical upper motor neuron signs, including increased tone, brisk reflexes, and muscle weakness with dysarthria and dysphagia. There was no sensory involvement as well as sphincter dysfunction and her cognition was contact.