Incidence of orolingual angioedema after intravenous thrombolysis for stroke.

INTRODUCTION: Orolingual angioedema (OA) is a known adverse effect of intravenous (i.v.) alteplase. We analyzed all patients treated with i.v. alteplase for stroke at our hospital since approval of i.v. thrombolysis in Italy in 2004 to assess the incidence of this complication. PATIENTS AND RESULTS: Four hundred thirty-three patients received alteplase for stroke from April 2004 to May 2017. Two women developed OA (0.4%; 95% confidence interval 0.1 to 1.6%). Angioedema was mild in one case and severe in the other, with massive swelling of the lips, tongue, and oropharyngeal mucosa, and oropharyngeal bleeding, requiring intubation. Neither patient used ACE-inhibitors. DISCUSSION: The incidence of orolingual angioedema was very low in our series. Although OA is usually mild, anaphylactoid reactions may rarely occur, because of the variable degree of activation of the complement system and kinin cascade caused by alteplase. In such instances, admission to neurointensive care may be required. Specific bradykinin antagonists or drugs that target the kallikrein-kinin system are beginning to be used in the more severe cases. Thus, doctors and nurses caring for acute stroke patients need to be able to recognize and treat this complication.

SOD1 activity and protective factors in familial ALS patients with L84F SOD1 mutation.

METHOD: The activity and amount of SOD1 in erythrocyte lysates and the plasma amino acid content were evaluated in four familial ALS patients bearing the L84F SOD1 mutation (fALS), in an asymptomatic family member with the mutation (L84F(5)), in sporadic ALS patients (sALS) and controls. Three of the fALS patients and the L84F(5) subject were tested once a year for three consecutive years. RESULTS: At the first evaluation SOD1 activity was similar in controls, sALS and fALS; the amount of SOD1 protein was lower (P < 0.01) in fALS. In the subsequent 2 years, 34% and 52% decrease of SOD1 activity was recorded in fALS patients. The plasma amino acid pattern did not differ between controls and sALS, whereas fALS patients displayed high levels of plasma aspartate and glutamate. Aspartate was in the normal range but glutamate was still elevated in the subsequent evaluations. The L84F(5) subject had remarkably low levels of aspartate, glutamate and branched-chain amino acids. CONCLUSIONS: The method of measuring mutant SOD1 amount is indirect but the results are indicative of a reduction of mutant SOD1 taking place during fast-worsening phases of the disease. Since the disease onset of fALS patients is 42.8 +/- 11.3 years and the L84F(5) family member is asymptomatic at the age of 66, low levels of excitotoxic and branched-chain amino acids in plasma may constitute a protective factor against disease development.

Migraine with aura and white matter abnormalities: Notch3 mutation.

The authors report on an Italian family with eight affected members who show autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic aura. These symptoms are associated with white matter abnormalities on brain MRI. All living affected members carry a Notch3 mutation (Arg153Cys) previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). White matter abnormalities occur in a variable percentage of the general migraine population; CADASIL should be suspected in migraineurs with prolonged atypical aura and white matter abnormalities.

Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation.

OBJECTIVE: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area. BACKGROUND: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy. METHODS: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area. The authors also determined SOD1 activity in erythrocytes and lymphocytes. RESULTS: The three families included a total of 28 affected members distributed over six generations. Despite a wide variability in age at onset and disease duration, the clinical pattern is uniform, with onset in the lower limbs, ascending progression, and predominant lower motor neuron involvement in all subjects. Generational anticipation is evident in the last two generations. All familial ALS patients and one of the six sporadic patients carry the same L84F missense point mutation in exon 4 of the SOD1 gene. SOD1 enzyme activity and SOD1 protein levels were not decreased significantly in the L84F patients. CONCLUSION: The ALS patients carrying the L84F mutation derive from a common ancestor. This mutation is responsible for ALS clustering in the area. The L84F mutation does not modify SOD1-specific activity.